Carbohydrate-polymer conjugates for tunable protein binding on the blood brain barrier and methods of use

Abstract

The present invention relates to a carbohydrate-polymer conjugate comprising a repeat unit, a divalent linker, and a carbohydrate and compositions thereof, wherein the repeat unit comprises, in part, a linker and a carbohydrate, and a method comprising the step of administering a composition comprising the carbohydrate-polymer conjugate, wherein the composition can cross the blood-brain barrier.

Description

[0001] Attorney Docket No.206161-0065-00WO TITLE OF THE INVENTION CARBOHYDRATE-POLYMER CONJUGATES FOR TUNABLE PROTEIN BINDING ON THE BLOOD BRAIN BARRIER AND METHODS OF USE CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional App. No.63 / 634,117, filed on April 15, 2024, incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION In recent years, the utilization of nanoscale drug carriers (e.g., lipid nanoparticles, polymer-drug conjugates, polymeric nanoparticles) has generated significant interest due to their ability for selective targeting delivery of therapeutic cargo. However, the transportation of nanomaterials through low-permeability capillaries remains a substantial challenge. An especially challenging target is facilitating the movement of materials across the blood-brain barrier. Through passive diffusion, only hydrophobic molecules <500 Da are permeable. While select therapeutic drugs meet this criterion, this prohibitory behavior has made central nervous system (CNS) disorders particularly difficult to treat with classic pharmacological techniques and drastically limits the current scope of applications. While few molecular species can cross the BBB via passive diffusion, active transport mechanisms will readily move biologically relevant molecules across this barrier. Some examples are ions such as sodium or potassium, amino acids, certain peptides / proteins, and carbohydrates. Varied supramolecular architectures have been employed, such as inorganic nanoparticles, liposomes, polymeric nanoparticles, viral vectors, and peptide-conjugated drugs. Even though these techniques have been proven conceptually possible, they have historically suffered from low delivery efficacy and suggest there is significant room for improvement. The blood-brain barrier (BBB) is incredibly restrictive and serves as a structural and chemical barrier between the brain and systemic circulation. The BBB protects the brain from variations in blood composition and toxic materials and is required to be highly selective. Currently, molecules such as hydrophobic molecules smaller than ~500 Da and very small molecules such as gases (i.e. carbon dioxide and oxygen) can only cross the BBB through Attorney Docket No.206161-0065-00WO passive diffusion, whereas small biomolecules, nutrients, molecules with corresponding receptors can cross the BBB through active transport. Thus, there is a need in the art for materials which can actively move and transport across the blood-brain barrier. The present invention addresses this need. SUMMARY OF THE INVENTION The present invention relates to, in part, a method comprising the step of administering to a subject a composition comprising a carbohydrate-polymer conjugate comprising a structure represented by Formula (I): wherein: A represents a repeat unit selected from the group consisting of C5-C7alkyl, C5-C7heteroalkyl, C5-C7aryl, C5-C7heteroaryl, and C5-C7cycloalkyl; n represents an integer from 2- 500; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate; and wherein the carbohydrate-polymer conjugate crosses the blood-brain barrier. In some embodiments, the composition further comprises a therapeutic agent. In some embodiments, the therapeutic agent is selected from the group consisting of a small molecule, an anticancer agent, an antibody, an immunomodulatory agent, a chelating agent, an imaging agent, and combinations thereof. In some embodiments, the composition delivers the therapeutic agent across the blood brain barrier of the subject. Attorney Docket No.206161-0065-00WO In some embodiments, the composition binds to a glucose transporter. In some embodiments, the composition binds to GLUT-1. In some embodiments, A comprises one of the following structures: O, S, NR1, or CR2R3; R1, R2, and R3each independently represent a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30 alkyl, C1-C30 alkyl halide, C1-C30 alkoxy, and any combination thereof; and each structure is independently optionally further substituted. In some embodiments, L comprises a C1-C30alkyl which is optionally further substituted. In some embodiments, L is represented by one of the following structures:

[0002] Attorney Docket No.206161-0065-00WO to the carbohydrate; and R’ represents a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30 alkyl, C1-C30 alkyl halide, C1-C30 alkoxy, and any combination thereof. In some embodiments, the carbohydrate is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, and any combination thereof. In some embodiments, the carbohydrate is selected from the group consisting of glucose, mannose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, and any stereochemical isomer thereof. In some embodiments, the carbohydrate is glucose. In some embodiments, the carbohydrate-polymer conjugate is a copolymer comprising a repeating unit of at least two monomers, wherein at least one monomer comprises glucose. In some embodiments, L forms a direct bond to the C1-, C3-, or C6- hydroxyl group of the carbohydrate. In some embodiments, n is between 2 and 100. In some embodiments, the carbohydrate-polymer conjugate comprises the following structure: Attorney Docket No.206161-0065-00WO n . In some polymer conjugate comprises the following structure: n . The present invention in part, a method for eliciting a therapeutic effect of a therapeutic agent, comprising administering to a subject in need thereof a composition comprising a therapeutic agent and a carbohydrate-polymer conjugate comprising a structure represented by Formula (I): Formula (I) Attorney Docket No.206161-0065-00WO wherein: A represents a repeat unit selected from the group consisting of C5-C7 alkyl, C5-C7 heteroalkyl, C5-C7aryl, C5-C7heteroaryl, and C5-C7cycloalkyl; n represents an integer from 2- 500; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate; wherein the composition delivers the therapeutic agent across the blood brain barrier. In some embodiments, the subject has a central nervous system disorder selected from the group consisting of depression, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, stroke, head trauma, spinal cord injury, multiple sclerosis, dementia with Lewy Bodies, retinal degeneration, epilepsy, psychiatric disorders, disorders of hormonal balance, and cochlear degeneration. In some embodiments, the subject has a tumor of the central nervous system (CNS) selected from the group consisting of astrocytomas, glioblastomas, oligodendrogliomas, ependymomas, meningiomas, schwannomas, pituitary tumors, lymphomas, and secondary CNS tumors. The present invention further relates to, in part, a carbohydrate-polymer conjugate comprising a structure represented by Formula (I): wherein: A represents a repeat unit selected from the group consisting of C5-C7alkyl, C5-C7heteroalkyl, C5-C7 aryl, C5-C7 heteroaryl, and C5-C7 cycloalkyl; n represents an integer from 2-9; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate. Attorney Docket No.206161-0065-00WO BRIEF DESCRIPTION OF THE DRAWINGS The following detailed description of embodiments of the invention will be better understood when read in conjunction with the appended drawings. It should be understood that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings. Fig.1, comprising Fig.1A through Fig.1C, depicts the design and synthesis of carbohydrate-polymer conjugates (CPCs). Fig.1A depicts the structure of galactose-based monomers (left) and lactose-based monomers (right). Fig.1B depicts a general ring opening polymerization scheme of glycomonomers to afford CPCs in a single step. Fig.1C depicts1H- NMR analysis of the polymerization of mono-Gal7. Disappearance of the monomer alkene peak (orange) and appearance of two nonequivalent polymer alkene peaks (blue) indicate complete conversion Fig.2, comprising Fig.2A through Fig.2C, depicts nuclear magnetic resonance (NMR) spectra of kinetics studies. Fig.2A depicts representative kinetics1H NMR of mono-OH at various intervals. The blue box highlights the monomer alkene peak, the purple box highlights the polymer alkene peak, and the green box highlights the DMF-d7peak. Fig.2B depicts representative kinetics1H NMR of mono-Gal7 at various intervals. The blue box highlights the monomer alkene peak, the purple box highlights the polymer alkene peak, and the green box highlights the DMF-d7peak. Fig.2C depicts representative kinetics1H NMR of mono-Lac7at various intervals. The blue box highlights the monomer alkene peak, the purple box highlights the polymer alkene peak, and the green box highlights the DMF-d7peak. Fig.3, comprising Fig.3A through Fig.3D, depicts size exclusion chromatography-multiangle light scattering (SEC-MALS) data. Fig.3A depicts SEC-MALS data for polymerization kinetics experiments. Fig.3B depicts SEC-MALS data for polymers used in microscale thermophoresis (MST) experiments. Fig.3C depicts SEC-MALS data for polymers used to confirm computational analysis. Fig.3D depicts SEC-MALS data for polymers used in biological experiments. Fig.4 depicts a general synthetic pathway to access glycomonomers. (i) TEA, Toluene, Reflux, 12 h. (ii) TBS-Cl, TEA, DCM, rt, 12 h. (iii) DCC, DMAP, 0 °C to rt, 12 h, Attorney Docket No.206161-0065-00WO 71%-77%. (iv) AcCl, dry MeOH, rt, 12 h, 67%-91%. (v) BF3•Et2O, dry DCM, 0 °C to rt, 12 h. (vi) NaOMe, MeOH, rt, 4 h, 31%-40%. Fig.5, comprising Fig.5A and Fig.5B, depicts the effect of glycan density on Galactin-3 (Gal-3) binding. Fig.5A depicts a general chemical structure of copolymers with decreased galactose density. Fig.5B depicts calculated Kd values for the Gal-3 binding of Gal- CPCs at DP = 50, 100, and 250, as well as Co-CPC-50% and Co-CPC-20%. Fig.6, comprising Fig.6A through Fig.6C, depicts Coarse-Grained Molecular Dynamics analyses. Fig.6A depicts a representative schematic for the collapse of CPCs during the initial 50 ns of the simulation trajectory. The hydrophobic norbornene backbone is presented in red, whereas the carbohydrate functional groups are presented in cyan. Fig.6B depicts a radial distribution function (RDF) between centers-of-mass (COMs) of attached monosaccharide groups on the CPCs, calculated for the last 150 ns of the simulation run. Fig. 6C depicts the evolution of the nonbonded interaction energy between monosaccharide groups and water throughout the simulation run. Fig.7, comprising Fig.7A through Fig.7C, depicts representative data over simulations. Fig.7A depicts evolution of Rgof the entire CPC over the entire simulation run. Fig.7B depicts Rgdistribution for the entire CPC. Fig.7C depicts Rgdistribution for the backbone calculated for the last 150 ns of the simulation. All data is averaged over three simulations. Mean equilibrium values are included in the plots. Fig.8, comprising Fig.8A through Fig.8C, depicts radial distribution functions (RDFs). Fig.8A depicts RDFs between water and COM of carbohydrate groups. Fig.8B depicts RDFs between water and CPC backbone beads. Fig.8C depicts RDFs between water and RDF between carbohydrate groups. Legends included in the plots. Fig.9, comprising Fig.9A through Fig.9C, depicts solvent accessible surface areas (SASA) for CPCs. Fig.9A depicts evolution of SASA of the entire CPC over the entire simulation run. Fig.9B depicts a SASA distribution for the CPC backbone. Fig.9C depicts a SASA distribution for the CPC sidechains calculated for the last 150 ns of the simulation run. All plotted data is averaged over three simulation runs. Fig.10, comprising Fig.10A through Fig.10C, depicts evolution of nonbonded energy. Fig.10A depicts evolution of nonbonded energy between CPC backbone and water. Fig. 10B depicts evolution of nonbonded energy between monosaccharide groups and water. Fig. Attorney Docket No.206161-0065-00WO 10C depicts evolution of nonbonded energy between monosaccharide groups, for the entire simulation run. Fig.11 depicts representative dynamic light scattering (DLS) traces of polymers disclosed in Fig.3C and Fig.3D. Fig.12 depicts a Galectin-3 western blot of 4T1 and LNCaP cells. Fig.13, comprising Fig.13A through Fig.13D, depicts interactions of CPCs with cancer cells. Fig.13A depicts live-cell confocal images showing cell internalization of Gal- CPCs by 4T1 cells, following 4 h incubation. Fig.13B depicts a plot of polymer cytotoxicity in Gal-3-negative LnCAP cells following 4 h incubation. Fig.13C depicts a plot of polymer cytotoxicity in Gal-3-positive 4T1 cells following 4 h incubation. Fig.13D depicts the effect of treatment on cancer cell proliferation, following 24 h incubation. Gal-CPCs effectively suppress cancer cell proliferation in gal-3-positive 4T1 cells. Statistical analysis was performed using an ordinary one-way ANOVA, where “**” represents a P value of <0.01, “***” represents a P value of <0.001, and “****” represents a P value of <0.0001. Fig.14, comprising Fig.14A through Fig.14C, depicts cell uptake and proliferation data. Fig.14A depicts polymer cell uptake at 20x magnification. Top.) Fluorescence images of 4T1 cells incubated with Gal-7-100-Cy5 (λex = 640 nm) and stained with CellBrite™ Steady 488 membrane stain (λex = 488 nm). Bottom.) Fluorescence images of 4T1 cells treated only with membrane stain (λex = 488 nm) and PBS. Scale bar set to 50 µm in the first and second columns and 100 µm in the overlayed column. Fig.14B depicts large scale cell uptake via a 5x5 grid of 20x images. Top.) Fluorescence images of 4T1 cells incubated with Gal-7-100-Cy5 (λex = 640 nm) and stained with CellBrite™ Steady 488 membrane stain (λex = 488 nm). Bottom.) Fluorescence images of 4T1 cells treated only with membrane stain (λex = 488 nm) and PBS. Scale bar set to 500 µm in the overlayed column. Fig.14C depicts cell proliferation data using glucose polymer and the effect of treatment on LNCaP cell proliferation, following 24 h incubation. Statistical analysis was performed using an unpaired, two-tailed, t-test, where “****” represents a P value of < 0.0001. Fig.15, comprising Fig.15A through Fig.15E, depicts antimigration activities of CPCs. Fig.15A depicts representative images of scratched 4T1 cells before treatment (left) and after 24 h incubation with various constructs (right). Cells were stained with crystal violet to enhance contrast. Fig.15B depicts all CPCs show dose-dependent inhibition of 4T1 cell Attorney Docket No.206161-0065-00WO migration. Fig.15C depicts a comparison of antimigration efficacy of CPCs at 10 µM. At this dose, all constructs are able to suppress the migration of 4T1 cells; however, Gal-CPCs significantly outperform all other treatment groups. Fig.15D depicts a comparison of antimigration efficacy of CPCs at 5 µM. Fig.15E depicts a comparison of antimigration efficacy of CPCs at 2.5 µM. Fig.16 depicts chemical structures of galactose, mannose, and glucose monomers. Fig.17 depicts a general polymerization scheme. Fig.18 depicts polymerization kinetics monitored by nuclear magnetic resonance spectroscopy (NMR). All exo monomers were rapidly and completely polymerized while endo monomers converted slowly. Fig.19 depicts rate constant measurements for polymerizations. Fig.20 depicts polymerization kinetics by gel permeation chromatography (GPC) at 60˚C polymerization conditions. Mannose polymerization occurs significantly faster than glucose and galactose. Fig.21 depicts representative GPC analysis of polymers. Fig.22 depicts additional GPC analysis of polymers at lower degrees of polymerization (DPs). Fig.23 depicts circular dichroism (CD) spectra of all polymers in distilled water. Fig.24 depicts CD of Exo-PNP-Gal as a function of temperature. Fig.25 depicts a full CD sweep of Exo-PNP-Gal. Fig.26 depicts dynamic light scattering (DLS) data and CD (secondary structure) data of Exo-PNP-Gal and Exo-PNP-Glc. Fig.27 depicts dynamic light scattering (DLS) data and CD (secondary structure) data of Exo-PNP-Mannose. Fig.28 depicts Endo-Gal (left) and Endo-Glc (right) both exhibit the same behavior upon dialysis. Fig.29 depicts data which indicates that Endo-Man fails to form higher order assemblies in solution. Fig.30 depicts DLS data and transmission electron microscopy (TEM) images of Exo-Gal-NAs (nanoassemblies). Attorney Docket No.206161-0065-00WO Fig.31 depicts DLS data of Exo-Gal-NAs as a function of temperature. Fig.32 depicts representative TEM images of all nanoassemblies. Fig.33 depicts infrared (IR) spectra of Exo-Gal and Exo-Glc polymers. Fig.34 depicts DLS data of Exo-Gal and Endo-Gal, Exo-Glc and Endo-Glc, and Exo-Man and Endo-Man as a function of solvent. Fig.35 depicts Nile Red incorporation into the polymers. Fig.36 depicts DLS data and representative visual images of exo and endo polymers combined with Nile Red. Fig.37 depicts lectin (PNA) binding analysis of Gal polymers by DLS. Fig.38 depicts lectin (RCA120) binding analysis of Gal polymers by DLS Fig.39 depicts lectin (ConA) binding analysis of Glc polymers by DLS. Fig.40 depicts lectin (ConA) binding analysis of Gal polymers by DLS. Fig.41 depicts representative data of polymer-lectin binding as measured by microscale thermophoresis. Fig.42 depicts representative data of cell uptake of polymers as measured by flow cytometry. Fig.43 depicts a representative summary of the present invention. Fig.44 depicts the upregulation of Gal-3 in cancer and other inflammatory diseases. Fig.45 depicts the role of Gal-3 in anti-cancer immunity. Fig.46 depicts a schematic describing the goal to develop CPCs that bind Gal-3 with high avidity and specificity with the hypothesis that the macromolecular structure and presentation of carbohydrates dictates the avidity of galectin-3 binding. Fig.47 depicts representative monomers. Fig.48 depicts a representative scheme for ROMP. Fig.49 depicts polymerization results of galactose containing glycomonomers. Fig.50 depicts polymerization results of lactose containing glycomonomers. Fig.51 depicts representative data which shows the acetylation of lactose enables higher DP polymerizations. Attorney Docket No.206161-0065-00WO Fig.52 depicts representative data which shows how Galactose-CPCs bind Gal-3 with micromolar affinity. The number of atoms between galactose and the polymer backbone significantly influences binding to Gal-3. Fig.53 depicts representative derivatives of monomers. Fig.54 depicts representative data displaying the difference in behavior between Endo-CPCs and Exo-CPCs. Fig.55 depicts a general synthetic pathway to access glycomonomer. (i) Benzaldehyde dimethyl acetal, CSA, ACN, rt, 12 h, 88% (ii) BzCl, pyridine, rt, 12 h, 91% (iii) TEA, Toluene, Reflux, 12 h, 87%. (iv) NIS, TMSOTf, dry DCM, - 40 °C, 2 h, 67%. (v) DTT, CSA, dry DCM, rt, 7 h. (vi) NaOMe, MeOH, rt, 2 h, 62% (2 steps). Fig.56, comprising Fig.56A through Fig.56C, depicts course-grain (CG) mapping schemes. Fig.56A depicts a CG mapping scheme for Co-CPC-50%. Fig.56B depicts a CG mapping scheme for Gal-CPC. Fig.56C depicts a CG mapping scheme for Lac-CPC. Fig.57, comprising Fig.57A through Fig.57A, depicts representative initial configurations. Fig.57A depicts a representative initial configuration for Co-CPC-50%. Fig. 57B depicts a representative initial configuration for Gal-CPC. Fig.57C depicts a representative initial configuration for Lac-CPC. Fig.58 depicts distributions of bond lengths obtained from CG MD simulations of β-galactose and β-glucose, and their corresponding mapped AA trajectories Fig.59 depicts distributions of angles obtained from CG MD simulations of β- galactose and β-glucose, and their corresponding AA trajectories. Fig.60, comprising Fig.60A and Fig.60B, depicts additional modeling for CPC systems. Fig.60A depicts representative final configurations for Co-CPC-50%, Gal-CPC, and Lac-CPC. Fig.60B depicts dihedral angle autocorrelation functions calculated for two major CPC backbone dihedrals. Legends included in the plots. Fig.61 depicts a representative experimental layout and the chemical structures of C1, C3, and C6 glucose variants used in instant experiments. Fig.62 depicts a representative synthetic scheme of the 1-linked glucose monomer. Fig.63 depicts a representative synthetic scheme of the 3-linked glucose monomer. Attorney Docket No.206161-0065-00WO Fig.64 depicts a representative synthetic scheme of the 6-linked glucose monomer. Fig.65 depicts representative polymerization data of the 1-linked glucose monomer. Fig.66 depicts hypothesized routes of nucleophilic addition and alternative route to synthesis of 3-azido glucose. Fig.67 depicts representative synthetic schemes for the hydrophilic and hydrophobic monomers. Fig.68 depicts an image of an exemplary flow cytometry set up and a representative experimental flowchart of sample preparation. GLUT1 mediation is indicated by a decrease in uptake in phloretin samples. Fig.69 depicts flow cytometry results of the 1 carbon linked glucose polymers at lengths 10, 50, and 100 incubated without phloretin for 1 hour. The results indicated that the 10mer was internalized greatest after 1 hour of incubation and that polymer uptake decreased upon phloretin incubation. Fig.70 depicts flow cytometry results of the 1 carbon linked glucose polymers at lengths 10, 50, and 100 incubated without phloretin for 4 hours. The results indicated that uptake of the 10mer was doubled whereas the 50 and 100mer showed no change. Fig.71 depicts an overlay of the flow cytometry results of the 1 carbon linked glucose polymers at lengths 10, 50, and 100 incubated with and without phloretin for 1 hour vs 4 hours. Fig.72 depicts polymerization results of the 3 carbon linked glucose polymer and an overlay of the flow cytometry results of the 1 carbon linked glucose and the 3 carbon linked glucose polymers at lengths 10, 50, and 100 incubated with and without phloretin for 1 hour. Results indicated that the 10mer showed a large difference in uptake with change in linkage at 1 hour incubation. DETAILED DESCRIPTION The present invention provides compositions and methods for the synthesis of a carbohydrate-polymer conjugate. In some embodiments, the invention provides a carbohydrate- polymer conjugate comprising a ring comprising an olefin, a divalent linking group, and a Attorney Docket No.206161-0065-00WO carbohydrate. In some embodiments, the invention provides a method of synthesizing the carbohydrate-polymer conjugate. In some embodiments, the invention provides a method of use of the carbohydrate-polymer conjugate. Definitions Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. As used herein, each of the following terms has the meaning associated with it in this section. The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. “About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods. As used herein, the term “organic” includes polymeric materials as well as small molecule organic materials. “Small molecule” refers to any organic material that is not a polymer, and “small molecules” may actually be quite large. Small molecules may include repeat units in some circumstances. For example, using a long chain alkyl group as a substituent does not remove a molecule from the “small molecule” class. Small molecules may also be incorporated into polymers, for example as a pendent group on a polymer backbone or as a part of the backbone. Small molecules may also serve as the core moiety of a dendrimer, which consists of a series of chemical shells built on the core moiety. As used herein, the term “alkyl,” by itself or as part of another substituent means, unless otherwise stated, a straight or branched chain hydrocarbon having the number of carbon atoms designated (i.e. C1-6 means one to six carbon atoms) and including straight, branched chain, or cyclic substituent groups. Examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl, hexyl, and cyclopropylmethyl. Attorney Docket No.206161-0065-00WO As used herein, the term “substituted alkyl” means alkyl as defined above, substituted by one, two or three substituents selected from the group consisting of halogen, -OH, alkoxy, -NH2, amino, azido, -N(CH3)2, -C(=O)OH, trifluoromethyl, -C≡N, -C(=O)O(C1- C4)alkyl, -C(=O)NH2, -SO2NH2, -C(=NH)NH2, and -NO2. Examples of substituted alkyls include, but are not limited to, 2,2-difluoropropyl, 2-carboxycyclopentyl and 3-chloropropyl. As used herein, the term “olefin” encompasses compounds having a C=C bond. The term "olefin-based polymer," as used herein, refers to a polymer that contains at least a majority weight percent, based on the weight of the polymer, polymerized olefin (for example, ethylene or propylene), and, optionally, one or more additional comonomers. As used herein, the term “heteroalkyl” by itself or in combination with another term means, unless otherwise stated, a stable straight or branched chain alkyl group consisting of the stated number of carbon atoms and one or two heteroatoms selected from the group consisting of O, N, and S, and wherein the nitrogen and sulfur atoms may be optionally oxidized and the nitrogen heteroatom may be optionally quaternized. The heteroatom(s) may be placed at any position of the heteroalkyl group, including between the rest of the heteroalkyl group and the fragment to which it is attached, as well as attached to the most distal carbon atom in the heteroalkyl group. Examples include -O-CH2-CH2-CH3, -CH2-CH2-CH2-OH, -CH2-CH2-NH-CH3, -CH2-S-CH2-CH3, and -CH2CH2-S(=O)-CH3. Up to two heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3, or -CH2-CH2-S-S-CH3. As used herein, the term “alkoxy” employed alone or in combination with other terms means, unless otherwise stated, an alkyl group having the designated number of carbon atoms, as defined above, connected to the rest of the molecule via an oxygen atom, such as, for example, methoxy, ethoxy, 1-propoxy, 2-propoxy (isopropoxy) and the higher homologs and isomers. As used herein, the term “halo” or “halogen” alone or as part of another substituent means, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom. As used herein, the term “cycloalkyl” refers to a mono cyclic or polycyclic non- aromatic radical, wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom. In some embodiments, the cycloalkyl group is saturated or partially unsaturated. In another embodiment, the cycloalkyl group is fused with an aromatic ring. Cycloalkyl groups Attorney Docket No.206161-0065-00WO include groups having from 3 to 10 ring atoms. Illustrative examples of cycloalkyl groups include, but are not limited to, the following moieties: . cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Dicyclic cycloalkyls include, but are not limited to, tetrahydronaphthyl, indanyl, and tetrahydropentalene. Polycyclic cycloalkyls include adamantine and norbornane. The term cycloalkyl includes “unsaturated nonaromatic carbocyclyl” or “nonaromatic unsaturated carbocyclyl” groups, both of which refer to a nonaromatic carbocycle as defined herein, which contains at least one carbon double bond or one carbon triple bond. As used herein, the term “heterocycloalkyl” or “heterocyclyl” or “heterocyclic” refers to a cyclic group containing one to four ring heteroatoms each selected from O, S, and N. In some embodiments, each heterocycloalkyl group has from 4 to 10 atoms in its ring system, with the proviso that the ring of said group does not contain two adjacent O atoms. In another embodiment, the heterocycloalkyl group is fused with an aromatic ring. In some embodiments, the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen atom may be optionally quaternized. The heterocyclic system may be attached, unless otherwise stated, at any heteroatom or carbon atom that affords a stable structure. A heterocycle may be aromatic or non-aromatic in nature. In some embodiments, the heterocycle is a heteroaryl. An example of a 3-membered heterocycloalkyl group includes, and is not limited to, aziridine. Examples of 4-membered heterocycloalkyl groups include, and are not limited to, azetidine and a beta lactam. Examples of 5-membered heterocycloalkyl groups include, and are not limited to, pyrrolidine, oxazolidine and thiazolidinedione. Examples of 6-membered heterocycloalkyl groups include, and are not limited to, piperidine, morpholine and piperazine. Attorney Docket No.206161-0065-00WO Examples of non-aromatic heterocycles include monocyclic groups such as aziridine, oxirane, thiirane, azetidine, oxetane, thietane, pyrrolidine, pyrroline, pyrazolidine, imidazoline, dioxolane, sulfolane, 2,3-dihydrofuran, 2,5-dihydrofuran, tetrahydrofuran, thiophane, piperidine, 1,2,3,6-tetrahydropyridine, 1,4-dihydropyridine, piperazine, morpholine, thiomorpholine, pyran, 2,3-dihydropyran, tetrahydropyran, 1,4-dioxane, 1,3-dioxane, homopiperazine, homopiperidine, 1,3-dioxepane, 4,7-dihydro-1,3-dioxepin, and hexamethyleneoxide. As used herein, the term “aromatic” refers to a carbocycle or heterocycle with one or more polyunsaturated rings and having aromatic character, i.e. having (4n + 2) delocalized π (pi) electrons, where n is an integer. As used herein, the term “aryl,” employed alone or in combination with other terms, means, unless otherwise stated, a carbocyclic aromatic system containing one or more rings (typically one, two or three rings), wherein such rings may be attached together in a pendent manner, such as a biphenyl, or may be fused, such as naphthalene. Examples of aryl groups include phenyl, anthracyl, and naphthyl. As used herein, the term “aryl-(C1-C3)alkyl” means a functional group wherein a one- to three-carbon alkylene chain is attached to an aryl group, e.g., -CH2CH2- phenyl, –CH2- phenyl (benzyl), aryl-CH2- and aryl-CH(CH3)-. The term “substituted aryl-(C1-C3)alkyl” means an aryl-(C1-C3)alkyl functional group in which the aryl group is substituted. Similarly, the term “heteroaryl-(C1-C3)alkyl” means a functional group wherein a one to three carbon alkylene chain is attached to a heteroaryl group, e.g., -CH2CH2-pyridyl. The term “substituted heteroaryl-(C1-C3)alkyl” means a heteroaryl-(C1-C3)alkyl functional group in which the heteroaryl group is substituted. As used herein, the term “heteroaryl” or “heteroaromatic” refers to aryl groups which contain at least one heteroatom selected from N, O, Si, P, and S; wherein the nitrogen and sulfur atoms may be optionally oxidized, and the nitrogen atom(s) may be optionally quaternized. Heteroaryl groups may be substituted or unsubstituted. A heteroaryl group may be attached to the remainder of the molecule through a heteroatom. A polycyclic heteroaryl may include one or more rings that are partially saturated. Examples include tetrahydroquinoline, 2,3-dihydrobenzofuryl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4- imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4- Attorney Docket No.206161-0065-00WO isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3- thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2- benzimidazolyl, 5-indolyl, 1-isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3- quinolyl, and 6-quinolyl. Examples of non-aromatic heterocycles include monocyclic groups such as aziridine, oxirane, thiirane, azetidine, oxetane, thietane, pyrrolidine, pyrroline, imidazoline, pyrazolidine, dioxolane, sulfolane, 2,3-dihydrofuran, 2,5-dihydrofuran, tetrahydrofuran, thiophane, piperidine, 1,2,3,6-tetrahydropyridine, 1,4-dihydropyridine, piperazine, morpholine, thiomorpholine, pyran, 2,3-dihydropyran, tetrahydropyran, 1,4-dioxane, 1,3-dioxane, homopiperazine, homopiperidine, 1,3-dioxepane, 4,7-dihydro-1,3-dioxepin and hexamethyleneoxide. Examples of heteroaryl groups also include pyridyl, pyrazinyl, pyrimidinyl (particularly 2- and 4-pyrimidinyl), pyridazinyl, thienyl, furyl, pyrrolyl (particularly 2-pyrrolyl), imidazolyl, thiazolyl, oxazolyl, pyrazolyl (particularly 3- and 5-pyrazolyl), isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,3,4-thiadiazolyl and 1,3,4-oxadiazolyl. Examples of polycyclic heterocycles and heteroaryls include indolyl (particularly 3-, 4-, 5-, 6- and 7-indolyl), indolinyl, quinolyl, tetrahydroquinolyl, isoquinolyl (particularly 1- and 5-isoquinolyl), 1,2,3,4-tetrahydroisoquinolyl, cinnolinyl, quinoxalinyl (particularly 2- and 5-quinoxalinyl), quinazolinyl, phthalazinyl, 1,8-naphthyridinyl, 1,4-benzodioxanyl, coumarin, dihydrocoumarin, 1,5-naphthyridinyl, benzofuryl (particularly 3-, 4-, 5-, 6- and 7-benzofuryl), 2,3-dihydrobenzofuryl, 1,2-benzisoxazolyl, benzothienyl (particularly 3-, 4-, 5-, 6-, and 7-benzothienyl), benzoxazolyl, benzothiazolyl (particularly 2-benzothiazolyl and 5-benzothiazolyl), purinyl, benzimidazolyl (particularly 2-benzimidazolyl), benzotriazolyl, thioxanthinyl, carbazolyl, carbolinyl, acridinyl, pyrrolizidinyl, and quinolizidinyl. As used herein, the term “substituted” means that an atom or group of atoms has replaced hydrogen as the substituent attached to another group. The term “substituted” further refers to any level of substitution, namely mono-, di-, tri-, tetra-, or penta-substitution, where such substitution is permitted. The substituents are independently selected, and substitution may be at any chemically accessible position. In some embodiments, the substituents vary in number Attorney Docket No.206161-0065-00WO between one and four. In another embodiment, the substituents vary in number between one and three. In yet another embodiment, the substituents vary in number between one and two. As used herein, the term “optionally substituted” means that the referenced group may be substituted or unsubstituted. In some embodiments, the referenced group is optionally substituted with zero substituents, i.e., the referenced group is unsubstituted. In another embodiment, the referenced group is optionally substituted with one or more additional group(s) individually and independently selected from groups described herein. In some embodiments, the substituents are independently selected from the group consisting of oxo, halogen, -CN, -NH2, -OH, -NH(CH3), -N(CH3)2, alkyl (including straight chain, branched and / or unsaturated alkyl), substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, fluoroalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkoxy, fluoroalkoxy, -S-alkyl, S(=O)2alkyl, S(=O)2N[H, alkyl, or aryl], - C(=O)NH[substituted or unsubstituted alkyl, or substituted or unsubstituted phenyl], - C(=O)N[H or substituted or unsubstituted alkyl or aryl]2, -OC(=O)N[substituted or unsubstituted alkyl]2, -NHC(=O)NH[substituted or unsubstituted alkyl, or substituted or unsubstituted phenyl], -NHC(=O)alkyl, -N[substituted or unsubstituted alkyl]C(=O)[substituted or unsubstituted alkyl], -NHC(=O)[substituted or unsubstituted alkyl], -C(OH)[substituted or unsubstituted alkyl]2, and -C(NH2)[substituted or unsubstituted alkyl]2. In another embodiment, by way of example, an optional substituent is selected from oxo, fluorine, chlorine, bromine, iodine, -CN, -NH2, -OH, -NH(CH3), -N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, -CF3, -CH2CF3, - OCH3, -OCH2CH3, -OCH(CH3)2, -OCF3, - OCH2CF3, -S(=O)2-CH3, -C(=O)NH2, -C(=O)- NHCH3, -NHC(=O)NHCH3, -C(=O)CH3, -ON(O)2, and -C(=O)OH. In yet one embodiment, the substituents are independently selected from the group consisting of C1-6alkyl, -OH, C1-6alkoxy, halo, amino, acetamido, oxo and nitro. As used herein, where a substituent is an alkyl or alkoxy group, the carbon chain may be branched, straight or cyclic. As used herein, the term “protected,” as used herein, refers to the presence of a “protecting group” or moiety that prevents reaction of the chemically reactive functional group under certain reaction conditions. The protecting group will vary depending on the type of chemically reactive group being protected. By way of example only, (i) if the chemically reactive group is an amine or a hydrazide, the protecting group may be selected from tert- butyloxycarbonyl (t-Boc) and 9-fluorenylmethoxycarbonyl (Fmoc); (ii) if the chemically Attorney Docket No.206161-0065-00WO reactive group is a thiol, the protecting group may be orthopyridyldisulfide; and (iii) if the chemically reactive group is a carboxylic acid, such as butanoic or propionic acid, or a hydroxyl group, the protecting group may be benzyl or an alkyl group such as methyl, ethyl, or tert-butyl. Additionally, protecting groups include, but are not limited to, photolabile groups, such as Nvoc and MeNvoc, and other protecting groups known in the art. Other protecting groups are described in Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, N.Y., 1999. The term “derivative” refers to a small molecule that differs in structure from the reference molecule but retains the essential properties of the reference molecule. A derivative may change its interaction with certain other molecules relative to the reference molecule. A derivative molecule may also include a salt, an adduct, tautomer, isomer, or other variant of the reference molecule. The term “tautomers” are constitutional isomers of organic compounds that readily interconvert by a chemical process (tautomerization). The term “isomers” or “stereoisomers” refer to compounds, which have identical chemical constitution, but differ with regard to the arrangement of the atoms or groups in space. As used herein, the term “polymer” refers to a molecule composed of repeating structural units typically connected by covalent chemical bonds. The term “polymer” is also meant to include the terms copolymer and oligomers. As used herein, the term “polymerization” refers to at least one reaction that consumes at least one functional group in a monomeric molecule (or monomer), oligomeric molecule (or oligomer) or polymeric molecule (or polymer), to create at least one chemical linkage between at least two distinct molecules (e.g., intermolecular bond), at least one chemical linkage within the same molecule (e.g., intramolecular bond), or any combination thereof. A polymerization reaction may consume between about 0% and about 100% of the at least one functional group available in the system. In some embodiments, polymerization of at least one functional group results in about 100% consumption of the at least one functional group. In another embodiment, polymerization of at least one functional group results in less than about 100% consumption of the at least one functional group. As used herein, the term “polymer segment” means and includes a grouping of multiple monomer units of a single type (i.e., a homopolymer segment) or multiple types (i.e., a Attorney Docket No.206161-0065-00WO copolymer segment) of constitutional units into a continuous region of a polymer block that are of a length that is insufficient for microphase separation to inherently occur with other segments in the same block type. As used herein, the term “block copolymer” means and includes a polymer composed of chains where each chain contains two or more polymer blocks as defined above and at least two of the blocks are of sufficient segregation strength (e.g., χN>10) for those blocks to phase separate. A wide variety of block polymers are contemplated herein including diblock copolymers (i.e., polymers including two polymer blocks), triblock copolymers (i.e., polymers including three polymer blocks), multiblock copolymers (i.e., polymers including more than three polymer blocks), and combinations thereof. As used herein, a “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal's health continues to deteriorate. As used herein, a “disorder” in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal's state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal's state of health. As used herein with respect to the compositions of the invention, “biologically active” means that the compositions elicit a biological response in a mammal that can be monitored and characterized in comparison with an untreated mammal. As used herein, the term “treating” means ameliorating the effects of, or delaying, halting or reversing the progress of a disease or disorder. The word encompasses reducing the severity of a symptom of a disease or disorder and / or the frequency of a symptom of a disease or disorder. As used herein, the term “prevent” or “prevention” means no disorder or disease development if none had occurred, or no further disorder or disease development if there had already been development of the disorder or disease. Also considered is the ability of one to prevent some or all of the symptoms associated with the disorder or disease. Disease and disorder are used interchangeably herein. Attorney Docket No.206161-0065-00WO As used herein, the term “medical intervention” means a set of one or more medical procedures or treatments that are required for ameliorating the effects of, delaying, halting or reversing a disease or disorder of a subject. A medical intervention may involve surgical procedures or not, depending on the disease or disorder in question. A medical intervention may be wholly or partially performed by a medical specialist, or may be wholly or partially performed by the subject himself or herself, if capable, under the supervision of a medical specialist or according to literature or protocols provided by the medical specialist. As used herein, the terms “effective amount” or “therapeutically effective amount” or “pharmaceutically effective amount” of a composition are used interchangeably to refer to the amount of the composition that is sufficient to provide a beneficial effect to the subject to which the composition is administered. The term to “treat,” as used herein, means reducing the frequency with which symptoms are experienced by a patient or subject or administering a composition to reduce the severity with which symptoms are experienced. An appropriate therapeutic amount in any individual case may be determined by one of ordinary skill in the art using routine experimentation. By the term “specifically bind” or “specifically binds,” as used herein, is meant that a first molecule (e.g., an antibody) preferentially binds to a second molecule (e.g., a particular antigenic epitope), but does not necessarily bind only to that second molecule. As used herein, a “prophylactic” or “preventive” treatment is a treatment administered to a subject who does not exhibit signs of a disease or disorder or exhibits only early signs of the disease or disorder for the purpose of decreasing the risk of developing pathology associated with the disease or disorder. As used herein, a “therapeutic” treatment is a treatment administered to a subject who exhibits signs of pathology of a disease or disorder for the purpose of diminishing or eliminating those signs. As used herein, the term “pharmaceutically acceptable” refers to a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of the compound, and is relatively non-toxic, i.e., the material may be administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained. Attorney Docket No.206161-0065-00WO As used herein, a “pharmaceutically acceptable carrier” means a pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting a compound(s) of the present invention within or to the subject such that it can perform its intended function. Typically, such compounds are carried or transported from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation, and not injurious to the patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer’s solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations. As used herein “pharmaceutically acceptable carrier” also includes any and all coatings, antibacterial and antifungal agents, and absorption delaying agents, and the like that are compatible with the activity of the compound, and are physiologically acceptable to the subject. Supplementary active compounds can also be incorporated into the compositions. As used herein, the language “pharmaceutically acceptable salt” refers to a salt of the administered compounds prepared from pharmaceutically acceptable non-toxic acids, including inorganic acids, organic acids, solvates, hydrates, or clathrates thereof. As used herein, the term “subject” refers to a human or another mammal (e.g., primate, dog, cat, goat, horse, pig, mouse, rat, rabbit, and the like) that can have a disease, disorder, or condition; or be at risk for developing a disease, disorder, or condition; but may or may not have a disease, disorder, or condition or be at risk for developing a disease, disorder, or condition. In many embodiments of the present invention, the subject is a human being. In such embodiments, the subject is often referred to as an “individual” or a “patient.” The terms “individual” and “patient” do not denote a particular age. Attorney Docket No.206161-0065-00WO As used here, “biocompatible” refers to any material, which, when implanted in a mammal, does not provoke an adverse response in the mammal. A biocompatible material, when introduced into an individual, is not toxic or injurious to that individual, nor does it induce immunological rejection of the material in the mammal. The term “biodegradable” includes polymers, compositions and formulations, such as those described herein, that are intended to degrade during use. Biodegradable polymers typically differ from non-biodegradable polymers in that the former may be degraded during use. In some embodiments, such use involves in vivo use, such as in vivo therapy. In another embodiment, such use involves in vitro use. In general, biodegradation involves the degradation of a biodegradable polymer into its component subunits, or digestion, e.g., by a biochemical process, of the polymer into smaller, non-polymeric subunits. Two types of biodegradation may generally be identified. For example, biodegradation may involve cleavage of bonds (whether covalent or otherwise) in the polymer backbone. In such biodegradation, monomers and oligomers typically result, and even more typically, such biodegradation occurs by cleavage of a bond connecting one or more of subunits of a polymer. Further, biodegradation may involve cleavage of a bond (whether covalent or otherwise) internal to side chain or that connects a side chain to the polymer backbone. For example, a therapeutic agent or other chemical moiety attached as a side chain to the polymer backbone may be released by biodegradation. In some embodiments, at least one type of biodegradation may occur during use of a polymer. As used herein, the term “biodegradation” encompasses all known types of biodegradation. As used herein, the terms “biocompatible polymer” and “biocompatibility” when used in relation to polymers are recognized in the art. For example, biocompatible polymers include polymers that are generally neither toxic to the host, nor degrade (if the polymer degrades) at a rate that produces monomeric or oligomeric subunits or other byproducts at toxic concentrations in the host. In some embodiments, biodegradation generally involves degradation of the polymer in a host, e.g., into its monomeric subunits, which may be known to be effectively non-toxic. Intermediate oligomeric products resulting from such degradation may have different toxicological properties, however, or biodegradation may involve oxidation or other biochemical reactions that generate molecules other than monomeric subunits of the polymer. Consequently, in some embodiments, toxicology of a biodegradable polymer intended for in vivo use, such as implantation or injection into a patient, may be determined after one or Attorney Docket No.206161-0065-00WO more toxicity analyses. It is not necessary that any subject composition have a purity of 100% to be deemed biocompatible; indeed, it is only necessary that the subject compositions be biocompatible as set forth above. Hence, a subject composition may comprise polymers comprising 99%, 98%, 97%, 96%, 95%, 90%, 85%, 80%, 75% or even less of biocompatible polymers, e.g., including polymers and other materials and excipients described herein, and still be biocompatible. Several references to integers and R, R1, R2, R3, R4, R5, R6, etc. are made in chemical structures and moieties disclosed and described herein. Any description of integers and R, R1, R2, R3, R4, R5, R6, etc. in the specification is applicable to any structure or moiety reciting integers and R, R1, R2, R3, R4, R5, R6, etc. respectively. Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. Compounds and Carbohydrate-Polymer Conjugates The present invention relates to, in part, compounds and carbohydrate-polymer conjugates comprising a structure represented by Formula (I):

[0003] Attorney Docket No.206161-0065-00WO wherein: A represents a repeat unit selected from the group consisting of C5-C7alkyl, C5- C7 heteroalkyl, C5-C7 aryl, C5-C7 heteroaryl, and C5-C7 cycloalkyl; n represents an integer from 2-500; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate. In some embodiments, A comprises one of the following structures: wherein the wave line or CR2R3; wherein R1, R2, and R3each independently represent a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30alkyl, C1-C30alkyl halide, C1-C30alkoxy, and any combination thereof; and wherein each structure is independently optionally further substituted. In some embodiments, A is derived from a ring A. In some embodiments, ring A comprises a cycloalkyl. In some embodiments, ring A comprises a heterocycloalkyl. In some embodiments, ring A comprises an aryl. In some embodiments, ring A comprises at least one olefin. In some embodiments, ring A is further substituted. In some embodiments, the carbohydrate-polymer conjugate is represented by Formula (I). Attorney Docket No.206161-0065-00WO In some embodiments, ring A comprises a norbornene. In some embodiments, ring A comprises an olefin that is more reactive than norbornene. In some embodiments, ring A is in an endo-configuration. In some embodiments, ring A is in an exo-configuration. In some embodiments, ring A is a racemate. As used herein, the terms “endo-” and “exo-” define isomerism of organic compounds comprising a substituent in a bridged ring system. The prefix “endo” or a compound or moiety in an “endo-configuration” is defined to have the highest priority substituent closest, or “syn” to the longest bridge, whereas “exo” or a compound or moiety in an “exo- configuration” is defined to have the highest priority substituent close, or “anti” to the longest bridge. In some embodiments, n is an integer between about 1 and about 500, about 1 and about 500, about 5 and about 500, about 10 and about 500, about 20 and about 500, about 30 and about 500, about 40 and about 500, about 50 and about 500, about 60 and about 500, about 70 and about 500, about 80 and about 500, about 90 and about 500, about 100 and about 500, about 10 and about 400, about 10 and about 300, about 10 and about 200, about 10 and about 100, about 10 and about 50, about 50 and about 500, about 50 and about 400, about 50 and about 300, about 50 and about 200, about 50 and about 100, about 100 and about 1000, about 100 and about 400, about 100 and about 300, about 100 and about 200, about 1 and about 2, about 1 and about 5, about 2 and about 5, about 2 and about 10, or at least about 1, 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, or 500. In some embodiments, the polymer backbone is unsaturated. In some embodiments, the polymer backbone is rigid. In some embodiments, the polymer backbone is partially saturated. In some embodiments, the polymer backbone is saturated. In some embodiments, the polymer backbone is flexible. In some embodiments, the polymer backbone comprises one or more pendant hydroxyl groups. In some embodiments, the polymer backbone is functionalizable. In some embodiments, the polymer backbone has an end group comprising a compound selected from the group consisting of a fluorophore, a terminal alkene, a benzyl group, an amino group, a therapeutic small molecule, and combinations thereof. In some embodiments, the linker comprises an amino acid. In some embodiments, the linker comprises a glycol. In some embodiments, the linker is capable of hydrogen-bonding. In some embodiments, R’ is hydrogen. In some embodiments, R’ is an Attorney Docket No.206161-0065-00WO alkoxy group. In some embodiments, R’ participates in hydrogen bonding. In some embodiments, R’ participates in intramolecular hydrogen bonding. In some embodiments, R’ participates in intermolecular hydrogen bonding. In some embodiments, the linker comprises a C1-C30 alkyl. In some embodiments, L further comprises a heteroaryl. In some embodiments, L further comprises a triazole. In some embodiments, L forms a direct bond to C1, C3, or C6 of the carbohydrate. In some embodiments, L forms a direct bond to the C1-, C3-, or C6-hydroxyl group of the carbohydrate. In some embodiments, the linking group L is represented by one of the following structures: to the carbohydrate; and R’ represents a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30 alkyl, C1-C30 alkyl halide, C1-C30 alkoxy, and any combination thereof. In some embodiments, L comprises a C1-C30 alkyl which is optionally further substituted. In some embodiments, L comprises triazole. Attorney Docket No.206161-0065-00WO In some embodiments, the carbohydrate is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, and any combination thereof. Exemplary carbohydrates include, but are not limited to, monosaccharides including trioses (such as: ketotriose (dihydroxyacetone); aldotriose (glyceraldehyde)); tetroses which include: ketotetrose (such as: erythrulose) and aldotetroses (such as: erythrose, threose); pentoses which include: ketopentose (such as: ribulose, xylulose) aldopentose (such as: ribose, arabinose, xylose, lyxose), deoxy sugar (such as: deoxyribose); hexoses which include: ketohexose (such as: psicose, fructose, sorbose, tagatose), aldohexose (such as: allose, altrose, glucose, mannose, gulose, idose, galactose, talose), deoxy sugar (such as: fucose, fuculose, rhamnose); heptose (such as: sedoheptulose); octose; nonose (such as: neuraminic acid); disaccharides which include: sucrose; lactose; maltose; trehalose; turanose; cellobiose; kojiboise; nigerose; isomaltose; and palatinose; trisaccharides which include: melezitose; and maltotriose; oligosaccharides that include: corn syrups and maltodextrin; and polysaccharides that include: glucan (such as dextrin, dextran, beta-glucan), glycogen, mannan, galactan, and starch (such as those from corn, wheat, tapioca, rice, and potato, including amylose and amylopectin. The starches can be natural or modified or gelatinized); or combinations thereof. Carbohydrates also include source of sweeteners such as honey, maple syrup, glucose (dextrose), corn syrup, corn syrup solids, high fructose corn syrups, crystalline fructose, juice concentrates, dextrose polymers, malt syrup, rice syrup solids, sorghum syrup, refiner syrup, crystalline fructose, brown or invert sugars, molasses, or other grain / nut syrups consisting of rice syrup, agave syrup, palm syrup, and crystalline juice. In some embodiments, the carbohydrate is selected from the group consisting of galactose, glucose, mannose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, and any stereochemical isomer thereof. In some embodiments, the carbohydrate comprises glucose. In some embodiments, the carbohydrate comprises glucose. In some embodiments, the carbohydrate comprises mannose. In some embodiments, the carbohydrate is stereochemically pure. In some embodiments, the carbohydrate is a racemate. In some embodiments, the carbohydrate is partially stereochemically pure. In some embodiments, the carbohydrate is derived from commercially available sources. In some embodiments, the carbohydrate is extracted from food. Attorney Docket No.206161-0065-00WO In some embodiments, the carbohydrate is glucose. In some embodiments, * represents a bond to the carbohydrate at C1, C2, C3, C4, C5, C6, C1-hydroxyl, C2-hydroxyl, C3-hydroxyl, C4-hydroxyl, C5-hydroxyl, C6-hydroxyl, or any combination thereof. In some embodiments, the carbohydrate-polymer conjugate is further represented by one of the following structures: . In is a copolymer comprising a repeat unit of at least two monomers, wherein at least one monomer comprises glucose. In some embodiments, the carbohydrate-polymer conjugate is a block copolymer. Other exemplary copolymers which may describe the present invention include, but are not limited to, random copolymers, statistical copolymers, alternating copolymers, stereoblock copolymers, gradient copolymers, graft copolymers, star copolymers, and combinations thereof. In some embodiments, the carbohydrate-polymer conjugate comprises a monomer which does not comprise a carbohydrate. In some embodiments, the carbohydrate-polymer conjugate comprises a monomer which comprises a hydroxyl capped linker. In some embodiments, the carbohydrate-polymer conjugate comprises a monomer which comprises a linker bonded to a protecting group. In some embodiments, the carbohydrate is acetylated. In some embodiments, the carbohydrate-polymer conjugate forms higher order assemblies. In some embodiments, the carbohydrate-polymer conjugate forms secondary structures. In some embodiments, the carbohydrate-polymer conjugate comprises exposed hydrophobic pockets. In some embodiments, the carbohydrate-polymer conjugate forms nanoassemblies. In some embodiments, the carbohydrate-polymer conjugate forms higher order assemblies after dialysis. In some embodiments, the carbohydrate-polymer conjugate forms higher order assemblies after dialysis with DMSO. In some embodiments, the carbohydrate- Attorney Docket No.206161-0065-00WO polymer conjugate participates in intramolecular hydrogen bonding. In some embodiments, the carbohydrate-polymer conjugate participates in intermolecular hydrogen bonding. In some embodiments, the carbohydrate-polymer conjugate readily binds a protein target. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 5% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 10% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 15% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a graft density of about 20% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 30% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a graft density of about 40% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 50% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a graft density of about 60% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 70% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a graft density of about 80% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 90% to about 100%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 10% to about 90%. In some embodiments, the carbohydrate-polymer conjugate has a graft density of about 20% to about 90%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 30% to about 90%. In some embodiments, the carbohydrate-polymer conjugate has a graft density of about 40% to about 90%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 50% to about 90%. In some embodiments, the carbohydrate-polymer conjugate has a graft density of about 60% to about 90%. In some embodiments, the carbohydrate-polymer conjugate has a grafting density of about 70% to about 90%. In some embodiments, the carbohydrate- polymer conjugate has a graft density of about 80% to about 90%. In some embodiments, the carbohydrate-polymer conjugate is readily dissolved in a biorelevant medium. In some embodiments, the carbohydrate-polymer conjugate readily forms a suspension in a biorelevant medium. Compositions and Formulations of the Carbohydrate-Polymer Conjugate Attorney Docket No.206161-0065-00WO The present invention is further drawn to, in part, compositions and formulations comprising the carbohydrate-polymer conjugate. In some embodiments, the composition is a biodegradable composition. In some embodiments, the composition is a medical biodegradable composition. In some embodiments, the compositions and formulations further comprise a therapeutic agent. In some embodiments, the carbohydrate-polymer conjugate serves as a carrier for the therapeutic agent. In some embodiments, the therapeutic agent is selected from the group consisting of a small molecule, an anticancer agent, an antibody, an immunomodulatory agent, a chelating agent, an imaging agent, and combinations thereof. In some embodiments, the composition or formulation delivers the therapeutic agent across the blood brain barrier. Other exemplary therapeutic agents that may be employed in the compositions and formulations described herein include, but are not limited to, growth factors; monoclonal antibodies; immunomodulatory agents, including agents that cause T and B cell activation, proliferation, and / or maturation; agents that bring about innate immune system activation, proliferation and / or maturation (e.g., JNK, MAPK, ERK, NK kappa B pathway agonists or antagonists, and monocyte, neutrophil, or macrophage agonists or antagonists); matrix metalloproteinase inhibitors; heat shock protein agonists or antagonists; alpha synuclein inhibitors; chelating agents; diuretics; alpha 1 antitrypsin modulators; purinoceptor agonists or antagonists; cyclooxygenase 2 inhibitors; DNA gyrase inhibitors; natural killer cell and natural killer T cell agonists or antagonists; cathepsin class agonists or antagonists; antioxidant therapy agents; rho-associated kinase inhibitors; myosin inhibitors; phosphatidylinositol 3 kinase inhibitors and related molecules; nitric oxide synthase agonists or antagonists; nitric oxide agonists or antagonists; ion channel function or trafficking modulators; surfactants, in particular, lung surfactants; cannabinoid receptor modulators; complement system inhibitors; IgE receptor antagonists; G protein-coupled receptor agonists or antagonists; chemokines; chemokine receptor agonists or antagonists; cytokines; cytokine receptor agonists or antagonists; arachidonic acid agonists or antagonists; inflammation mediators; STAT6 inhibitors; histamine or leukotriene agonists or antagonists; calcineurin agonists or antagonists; and any combination thereof. In various aspects, the composition comprises: one or more polymers of the present invention and one or more stabilizers. In other aspects, the composition comprises: one Attorney Docket No.206161-0065-00WO or more nanoparticles of the present invention and one or more stabilizers. In various embodiments, the stabilizer to nanoparticle weight ratio is less than 50%. In some embodiments, the stabilizer comprises a biocompatible polymer. Examples of stabilizers include, but are not limited to, biocompatible polymer, a biodegradable polymer, a multifunctional linker, starch, modified starch, and starch derivatives, gums, including but not limited to polymers, polypeptides, albumin, amino acids, thiols, amines, carboxylic acid and combinations or derivatives thereof, citric acid, xanthan gum, alginic acid, other alginates, benitoniite, veegum, agar, guar, locust bean gum, gum arabic, quince psyllium, flax seed, okra gum, arabinoglactin, pectin, tragacanth, scleroglucan, dextran, amylose, amylopectin, dextrin, etc., cross-linked polyvinylpyrrolidone, ion-exchange resins, potassium polymethacrylate, carrageenan (and derivatives), gum karaya and biosynthetic gum, polycarbonates (linear polyesters of carbonic acid); microporous materials (bisphenol, a microporous poly(vinylchloride), micro-porous polyamides, microporous modacrylic copolymers, microporous styrene-acrylic and its copolymers); porous polysulfones, halogenated poly(vinylidene), polychloroethers, acetal polymers, polyesters prepared by esterification of a dicarboxylic acid or anhydride with an alkylene polyol, poly(alkylenesulfides), phenolics, polyesters, asymmetric porous polymers, cross-linked olefin polymers, hydrophilic microporous homopolymers, copolymers or interpolymers having a reduced bulk density, and other similar materials, poly(urethane), cross- linked chain-extended poly(urethane), poly(imides), poly(benzimidazoles), collodion, regenerated proteins, semi-solid cross-linked poly(vinylpyrrolidone), monomeric, dimeric, oligomeric or long-chain, copolymers, block polymers, block co-polymers, polymers, PEG, dextran, modified dextran, polyvinylalcohol, and polyvinylpyrollidone. The compositions are formulated in a pharmaceutically acceptable excipient, such as wetting agents, buffers, disintegrants, binders, fillers, flavoring agents and liquid carrier media such as sterile water, water / ethanol etc. The compositions should be suitable for administration either by topical administration or injection or inhalation or catheterization or instillation or transdermal introduction into any of the various body cavities including the alimentary canal, the vagina, the rectum, the bladder, the ureter, the urethra, the mouth, etc. For oral administration, the pH of the composition is preferably in the acid range (e.g., 2 to 7) and buffers or pH adjusting agents may be used. The contrast media may be formulated in Attorney Docket No.206161-0065-00WO conventional pharmaceutical administration forms, such as tablets, capsules, powders, solutions, dispersion, syrups, suppositories etc. The compounds, nanoparticles, or compositions of the invention can be formulated and administered to a subject, as now described. The invention encompasses the preparation and use of pharmaceutical compositions comprising the compound, nanoparticle, and / or compositions of the invention useful for the delivery of a therapeutic agent to a cell. The invention also encompasses the preparation and use of pharmaceutical compositions comprising the compound, nanoparticle, and / or compositions of the invention useful for the treatment of a disease or disorder. Such a pharmaceutical composition may consist of the active ingredient alone, in a form suitable for administration to a subject, or the pharmaceutical composition may comprise the active ingredient and one or more pharmaceutically acceptable carriers, one or more additional ingredients, or some combination of these. The active ingredient may be present in the pharmaceutical composition in the form of a physiologically acceptable ester or salt, such as in combination with a physiologically acceptable cation or anion, as is well known in the art. The pharmaceutical compositions useful for practicing the invention may be administered to deliver a dose of between about 0.01 ng / kg / day and 500 mg / kg / day. In various embodiments, the pharmaceutical compositions useful in the methods of the invention may be administered, by way of example, systemically, parenterally, or topically, such as, in oral formulations, inhaled formulations, including solid or aerosol, and by topical or other similar formulations. In addition to the appropriate therapeutic composition, such pharmaceutical compositions may contain pharmaceutically acceptable carriers and other ingredients known to enhance and facilitate drug administration. Other possible formulations, such as nanoparticles, liposomes, resealed erythrocytes, and immunologically based systems may also be used to administer an appropriate modulator thereof, according to the methods of the invention. Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for ethical administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals, patients, and subjects of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the Attorney Docket No.206161-0065-00WO compositions suitable for administration to various animals and patients is well understood, and the ordinarily skilled veterinary pharmacologist can design and perform such modification with merely ordinary, if any, experimentation. Pharmaceutical compositions that are useful in the methods of the invention may be prepared, packaged, or sold in formulations suitable for oral, rectal, vaginal, parenteral, topical, pulmonary, intranasal, buccal, intravenous, ophthalmic, intrathecal and other known routes of administration. Other contemplated formulations include projected nanoparticles, liposomal preparations, resealed erythrocytes containing the active ingredient, and immunologically-based formulations. A pharmaceutical composition of the invention may be prepared, packaged, or sold in bulk, as a single unit dose, or as a plurality of single unit doses. As used herein, a “unit dose” is discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage. The relative amounts of the active ingredient, the pharmaceutically acceptable carrier, and any additional ingredients in a pharmaceutical composition of the invention will vary, depending upon the identity, size, and condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100% (w / w) active ingredient. In addition to the active ingredient, a pharmaceutical composition of the invention may further comprise one or more additional pharmaceutically active agents. Controlled- or sustained-release formulations of a pharmaceutical composition of the invention may be made using conventional technology. A formulation of a pharmaceutical composition of the invention suitable for oral administration may be prepared, packaged, or sold in the form of a discrete solid dose unit including, but not limited to, a tablet, a hard or soft capsule, a cachet, a troche, or a lozenge, each containing a predetermined amount of the active ingredient. Other formulations suitable for oral administration include, but are not limited to, a powdered or granular formulation, an aqueous or oily suspension, an aqueous or oily solution, or an emulsion. Attorney Docket No.206161-0065-00WO A tablet comprising the active ingredient may, for example, be made by compressing or molding the active ingredient, optionally with one or more additional ingredients. Compressed tablets may be prepared by compressing, in a suitable device, the active ingredient in a free-flowing form such as a powder or granular preparation, optionally mixed with one or more of a binder, a lubricant, an excipient, a surface-active agent, and a dispersing agent. Molded tablets may be made by molding, in a suitable device, a mixture of the active ingredient, a pharmaceutically acceptable carrier, and at least sufficient liquid to moisten the mixture. Pharmaceutically acceptable excipients used in the manufacture of tablets include, but are not limited to, inert diluents, granulating and disintegrating agents, binding agents, and lubricating agents. Known dispersing agents include, but are not limited to, potato starch and sodium starch glycolate. Known surface active agents include, but are not limited to, sodium lauryl sulphate. Known diluents include, but are not limited to, calcium carbonate, sodium carbonate, lactose, microcrystalline cellulose, calcium phosphate, calcium hydrogen phosphate, and sodium phosphate. Known granulating and disintegrating agents include, but are not limited to, corn starch and alginic acid. Known binding agents include, but are not limited to, gelatin, acacia, pre-gelatinized maize starch, polyvinylpyrrolidone, and hydroxypropyl methylcellulose. Known lubricating agents include, but are not limited to, magnesium stearate, stearic acid, silica, and talc. Tablets may be non-coated or they may be coated using known methods to achieve delayed disintegration in the gastrointestinal tract of a subject, thereby providing sustained release and absorption of the active ingredient. By way of example, a material such as glyceryl monostearate or glyceryl distearate may be used to coat tablets. Further by way of example, tablets may be coated using methods described in U.S. Pat. Nos.4,256,108; 4,160,452; and 4,265,874 to form osmotically-controlled release tablets. Tablets may further comprise a sweetening agent, a flavoring agent, a coloring agent, a preservative, or some combination of these in order to provide pharmaceutically elegant and palatable preparation. Hard capsules comprising the active ingredient may be made using a physiologically degradable composition, such as gelatin. Such hard capsules comprise the active ingredient, and may further comprise additional ingredients including, for example, an inert solid diluent such as calcium carbonate, calcium phosphate, or kaolin. Attorney Docket No.206161-0065-00WO Soft gelatin capsules comprising the active ingredient may be made using a physiologically degradable composition, such as gelatin. Such soft capsules comprise the active ingredient, which may be mixed with water or an oil medium such as peanut oil, liquid paraffin, or olive oil. Liquid formulations of a pharmaceutical composition of the invention which are suitable for oral administration may be prepared, packaged, and sold either in liquid form or in the form of a dry product intended for reconstitution with water or another suitable vehicle prior to use. Liquid suspensions may be prepared using conventional methods to achieve suspension of the active ingredient in an aqueous or oily vehicle. Aqueous vehicles include, for example, water and isotonic saline. Oily vehicles include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin. Liquid suspensions may further comprise one or more additional ingredients including, but not limited to, suspending agents, dispersing or wetting agents, emulsifying agents, demulcents, preservatives, buffers, salts, flavorings, coloring agents, and sweetening agents. Oily suspensions may further comprise a thickening agent. Known suspending agents include, but are not limited to, sorbitol syrup, hydrogenated edible fats, sodium alginate, polyvinylpyrrolidone, gum tragacanth, gum acacia, and cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, and hydroxypropylmethylcellulose. Known dispersing or wetting agents include, but are not limited to, naturally-occurring phosphatides such as lecithin, condensation products of an alkylene oxide with a fatty acid, with a long chain aliphatic alcohol, with a partial ester derived from a fatty acid and a hexitol, or with a partial ester derived from a fatty acid and a hexitol anhydride (e.g. polyoxyethylene stearate, heptadecaethyleneoxycetanol, polyoxyethylene sorbitol monooleate, and polyoxyethylene sorbitan monooleate, respectively). Known emulsifying agents include, but are not limited to, lecithin and acacia. Known preservatives include, but are not limited to, methyl, ethyl, or n-propyl-para-hydroxybenzoates, ascorbic acid, and sorbic acid. Known sweetening agents include, for example, glycerol, propylene glycol, sorbitol, sucrose, and saccharin. Known thickening agents for oily suspensions include, for example, beeswax, hard paraffin, and cetyl alcohol. Attorney Docket No.206161-0065-00WO Liquid solutions of the active ingredient in aqueous or oily solvents may be prepared in substantially the same manner as liquid suspensions, the primary difference being that the active ingredient is dissolved, rather than suspended in the solvent. Liquid solutions of the pharmaceutical composition of the invention may comprise each of the components described with regard to liquid suspensions, it being understood that suspending agents will not necessarily aid dissolution of the active ingredient in the solvent. Aqueous solvents include, for example, water and isotonic saline. Oily solvents include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin. Powdered and granular formulations of a pharmaceutical preparation of the invention may be prepared using known methods. Such formulations may be administered directly to a subject, used, for example, to form tablets, to fill capsules, or to prepare an aqueous or oily suspension or solution by addition of an aqueous or oily vehicle thereto. Each of these formulations may further comprise one or more of dispersing or wetting agent, a suspending agent, and a preservative. Additional excipients, such as fillers and sweetening, flavoring, or coloring agents, may also be included in these formulations. A pharmaceutical composition of the invention may also be prepared, packaged, or sold in the form of oil-in-water emulsion or a water-in-oil emulsion. The oily phase may be a vegetable oil such as olive or arachis oil, a mineral oil such as liquid paraffin, or a combination of these. Such compositions may further comprise one or more emulsifying agents such as naturally occurring gums such as gum acacia or gum tragacanth, naturally-occurring phosphatides such as soybean or lecithin phosphatide, esters or partial esters derived from combinations of fatty acids and hexitol anhydrides such as sorbitan monooleate, and condensation products of such partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. These emulsions may also contain additional ingredients including, for example, sweetening or flavoring agents. Methods for impregnating or coating a material with a chemical composition are known in the art, and include, but are not limited to methods of depositing or binding a chemical composition onto a surface, methods of incorporating a chemical composition into the structure of a material during the synthesis of the material (i.e., such as with a physiologically degradable Attorney Docket No.206161-0065-00WO material), and methods of absorbing an aqueous or oily solution or suspension into an absorbent material, with or without subsequent drying. As used herein, “parenteral administration” of a pharmaceutical composition includes any route of administration characterized by physical breaching of a tissue of a subject and administration of the pharmaceutical composition through the breach in the tissue. Parenteral administration thus includes, but is not limited to, administration of a pharmaceutical composition by injection of the composition, by application of the composition through a surgical incision, by application of the composition through a tissue-penetrating non-surgical wound, and the like. In particular, parenteral administration is contemplated to include, but is not limited to, cutaneous, subcutaneous, intraperitoneal, intravenous, intramuscular, intracisternal injection, and kidney dialytic infusion techniques. Formulations of a pharmaceutical composition suitable for parenteral administration comprise the active ingredient combined with a pharmaceutically acceptable carrier, such as sterile water or sterile isotonic saline. Such formulations may be prepared, packaged, or sold in a form suitable for bolus administration or for continuous administration. Injectable formulations may be prepared, packaged, or sold in unit dosage form, such as in ampules or in multi-dose containers containing a preservative. Formulations for parenteral administration include, but are not limited to, suspensions, solutions, emulsions in oily or aqueous vehicles, pastes, and implantable sustained-release or biodegradable formulations. Such formulations may further comprise one or more additional ingredients including, but not limited to, suspending, stabilizing, or dispersing agents. In some embodiments of a formulation for parenteral administration, the active ingredient is provided in dry (i.e., powder or granular) form for reconstitution with a suitable vehicle (e.g., sterile pyrogen-free water) prior to parenteral administration of the reconstituted composition. The pharmaceutical compositions may be prepared, packaged, or sold in the form of a sterile injectable aqueous or oily suspension or solution. This suspension or solution may be formulated according to the known art, and may comprise, in addition to the active ingredient, additional ingredients such as the dispersing agents, wetting agents, or suspending agents described herein. Such sterile injectable formulations may be prepared using a non-toxic parenterally-acceptable diluent or solvent, such as water or 1,3-butane diol, for example. Other acceptable diluents and solvents include, but are not limited to, Ringer's solution, isotonic Attorney Docket No.206161-0065-00WO sodium chloride solution, and fixed oils such as synthetic mono- or di-glycerides. Other parentally-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form, in a liposomal preparation, or as a component of a biodegradable polymer systems. Compositions for sustained release or implantation may comprise pharmaceutically acceptable polymeric or hydrophobic materials such as an emulsion, an ion exchange resin, a sparingly soluble polymer, or a sparingly soluble salt. Formulations suitable for topical administration include, but are not limited to, liquid or semi-liquid preparations such as liniments, lotions, oil-in-water or water-in-oil emulsions such as creams, ointments or pastes, and solutions or suspensions. Topically- administrable formulations may, for example, comprise from about 1% to about 10% (w / w) active ingredient, although the concentration of the active ingredient may be as high as the solubility limit of the active ingredient in the solvent Formulations for topical administration may further comprise one or more of the additional ingredients described herein. A pharmaceutical composition of the invention may be prepared, packaged, or sold in a formulation suitable for pulmonary administration via the buccal cavity. Such a formulation may comprise dry particles which comprise the active ingredient and which have a diameter in the range from about 0.5 to about 7 nanometers, and preferably from about 1 to about 6 nanometers. Such compositions are conveniently in the form of dry powders for administration using a device comprising a dry powder reservoir to which a stream of propellant may be directed to disperse the powder or using a self-propelling solvent / powder-dispensing container such as a device comprising the active ingredient dissolved or suspended in a low- boiling propellant in a sealed container. Preferably, such powders comprise particles wherein at least 98% of the particles by weight have a diameter greater than 0.5 nanometers and at least 95% of the particles by number have a diameter less than 7 nanometers. More preferably, at least 95% of the particles by weight have a diameter greater than 1 nanometer and at least 90% of the particles by number have a diameter less than 6 nanometers. Dry powder compositions preferably include a solid fine powder diluent such as sugar and are conveniently provided in a unit dose form. Low boiling propellants generally include liquid propellants having a boiling point of below 65 °F at atmospheric pressure. Generally the propellant may constitute 50 to 99.9% (w / w) of the composition, and the active ingredient may constitute 0.1 to 20% (w / w) of Attorney Docket No.206161-0065-00WO the composition. The propellant may further comprise additional ingredients such as a liquid non-ionic or solid anionic surfactant or a solid diluent (preferably having a particle size of the same order as particles comprising the active ingredient). Pharmaceutical compositions of the invention formulated for pulmonary delivery may also provide the active ingredient in the form of droplets of a solution or suspension. Such formulations may be prepared, packaged, or sold as aqueous or dilute alcoholic solutions or suspensions, optionally sterile, comprising the active ingredient, and may conveniently be administered using any nebulization or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface-active agent, or a preservative such as methylhydroxybenzoate. The droplets provided by this route of administration preferably have an average diameter in the range from about 0.1 to about 200 nanometers. The formulations described herein as being useful for pulmonary delivery are also useful for intranasal delivery of a pharmaceutical composition of the invention. Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle from about 0.2 to 500 micrometers. Such a formulation is administered in the manner in which snuff is taken i.e. by rapid inhalation through the nasal passage from a container of the powder held close to the nares. Formulations suitable for nasal administration may, for example, comprise from about as little as 0.1% (w / w) and as much as 100% (w / w) of the active ingredient, and may further comprise one or more of the additional ingredients described herein. A pharmaceutical composition of the invention may be prepared, packaged, or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of tablets or lozenges made using conventional methods, and may, for example, contain 0.1 to 20% (w / w) active ingredient, the balance comprising an orally dissolvable or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations suitable for buccal administration may comprise a powder or an aerosolized or atomized solution or suspension comprising the active ingredient. Such powdered, aerosolized, or aerosolized formulations, when dispersed, preferably have an average Attorney Docket No.206161-0065-00WO particle or droplet size in the range from about 0.1 nanometers to about 2000 micrometers, and may further comprise one or more of the additional ingredients described herein. A pharmaceutical composition of the invention may be prepared, packaged, or sold in a formulation suitable for ophthalmic administration. Such formulations may, for example, be in the form of eye drops including, for example, a 0.1-1.0% (w / w) solution or suspension of the active ingredient in an aqueous or oily liquid carrier. Such drops may further comprise buffering agents, salts, or one or more other of the additional ingredients described herein. Other opthalmically-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form or in a liposomal preparation. As used herein, “additional ingredients” include, but are not limited to, one or more of the following: excipients; surface active agents; dispersing agents; inert diluents; granulating and disintegrating agents; binding agents; lubricating agents; sweetening agents; flavoring agents; coloring agents; preservatives; physiologically degradable compositions such as gelatin; aqueous vehicles and solvents; oily vehicles and solvents; suspending agents; dispersing or wetting agents; emulsifying agents, demulcents; buffers; salts; thickening agents; fillers; emulsifying agents; antioxidants; antibiotics; antifungal agents; stabilizing agents; and pharmaceutically acceptable polymeric or hydrophobic materials. Other “additional ingredients” which may be included in the pharmaceutical compositions of the invention are known in the art and described, for example in Genaro, ed., 1985, Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa. Typically dosages of the compound of the invention which may be administered to an animal or patient, preferably a human, range in amount from about 0.01 mg to about 100 g per kilogram of body weight of the animal or patient. While the precise dosage administered will vary depending upon any number of factors, including, but not limited to, the type of animal and type of disease state being treated, the age of the animal or patient and the route of administration. Preferably, the dosage of the compound will vary from about 0.01 mg to about 500 mg per kilogram of body weight of the animal or patient. The compound can be administered to an animal or patient as frequently as several times daily, or it can be administered less frequently, such as once a day, once a week, once every two weeks, once a month, or even less frequently, such as once every several months or even once a year or less. The frequency of the dose will be readily apparent to the skilled artisan and will depend upon Attorney Docket No.206161-0065-00WO any number of factors, such as, but not limited to, the type and severity of the disease being treated, the type and age of the animal, patient, etc. Administration of the compounds of the present invention or the compositions thereof may be continuous or intermittent, depending, for example, upon the recipient's physiological condition, whether the purpose of the administration is therapeutic or prophylactic, and other factors known to skilled practitioners. The administration of the agents of the invention may be essentially continuous over a preselected period of time or may be in a series of spaced doses. Both local and systemic administration is contemplated. The amount administered will vary depending on various factors including, but not limited to, the composition chosen, the particular disease, the weight, the physical condition, and the age of the mammal, and whether prevention or treatment is to be achieved. Such factors can be readily determined by the clinician employing animal models or other test systems which are well known to the art. One or more suitable unit dosage forms having the therapeutic agent(s) of the invention, which, as discussed below, may optionally be formulated for sustained release, can be administered by a variety of routes including parenteral, including by intravenous and intramuscular routes, as well as by direct injection into the diseased tissue. For example, the therapeutic agent may be directly injected into the muscle. The formulations may, where appropriate, be conveniently presented in discrete unit dosage forms and may be prepared by any of the methods well known to pharmacy. Such methods may include the step of bringing into association the therapeutic agent with liquid carriers, solid matrices, semi-solid carriers, finely divided solid carriers or combinations thereof, and then, if necessary, introducing or shaping the product into the desired delivery system. When the therapeutic agents of the invention are prepared for administration, they are preferably combined with a pharmaceutically acceptable carrier, diluent or excipient to form a pharmaceutical formulation, or unit dosage form. The total active ingredients in such formulations include from 0.1 to 99.9% by weight of the formulation. A “pharmaceutically acceptable” is a carrier, diluent, excipient, and / or salt that is compatible with the other ingredients of the formulation, and not deleterious to the recipient thereof. The active ingredient for administration may be present as a powder or as granules; as a solution, a suspension or an emulsion. Attorney Docket No.206161-0065-00WO Pharmaceutical formulations containing the therapeutic agents of the invention can be prepared by procedures known in the art using well-known and readily available ingredients. The therapeutic agents of the invention can also be formulated as solutions appropriate for parenteral administration, for instance by intramuscular, subcutaneous or intravenous routes. The pharmaceutical formulations of the therapeutic agents of the invention can also take the form of an aqueous or anhydrous solution or dispersion, or alternatively the form of an emulsion or suspension. Thus, the therapeutic agent may be formulated for parenteral administration (e.g., by injection, for example, bolus injection or continuous infusion) and may be presented in unit dose form in ampules, pre-filled syringes, small volume infusion containers or in multi-dose containers with an added preservative. The active ingredients may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Alternatively, the active ingredients may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization from solution, for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use. It will be appreciated that the unit content of active ingredient or ingredients contained in an individual aerosol dose of each dosage form need not in itself constitute an effective amount for treating the particular indication or disease since the necessary effective amount can be reached by administration of a plurality of dosage units. Moreover, the effective amount may be achieved using less than the dose in the dosage form, either individually, or in a series of administrations. The pharmaceutical formulations of the present invention may include, as optional ingredients, pharmaceutically acceptable carriers, diluents, solubilizing or emulsifying agents, and salts of the type that are well-known in the art. Specific non-limiting examples of the carriers and / or diluents that are useful in the pharmaceutical formulations of the present invention include water and physiologically acceptable buffered saline solutions, such as phosphate buffered saline solutions pH 7.0-8.0. In general, water, suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable Attorney Docket No.206161-0065-00WO carriers for parenteral solutions. Solutions for parenteral administration contain the active ingredient, suitable stabilizing agents and, if necessary, buffer substances. Antioxidizing agents such as sodium bisulfate, sodium sulfite or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium Ethylenediaminetetraacetic acid (EDTA). In addition, parenteral solutions can contain preservatives such as benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, a standard reference text in this field. The active ingredients of the invention may be formulated to be suspended in a pharmaceutically acceptable composition suitable for use in mammals and in particular, in humans. Such formulations include the use of adjuvants such as muramyl dipeptide derivatives (MDP) or analogs that are described in U.S. Patent Nos.4,082,735; 4,082,736; 4,101,536; 4,185,089; 4,235,771; and 4,406,890. Other adjuvants, which are useful, include alum (Pierce Chemical Co.), lipid A, trehalose dimycolate and dimethyldioctadecylammonium bromide (DDA), Freund’s adjuvant, and IL-12. Other components may include a polyoxypropylene- polyoxyethylene block polymer (Pluronic®), a non-ionic surfactant, and a metabolizable oil such as squalene (U.S. Patent No.4,606,918). Additionally, standard pharmaceutical methods can be employed to control the duration of action. These are well known in the art and include control release preparations and can include appropriate macromolecules, for example polymers, polyesters, polyamino acids, polyvinyl, pyrrolidone, ethylenevinylacetate, methyl cellulose, carboxymethyl cellulose or protamine sulfate. The concentration of macromolecules as well as the methods of incorporation can be adjusted in order to control release. Additionally, the agent can be incorporated into particles of polymeric materials such as polyesters, polyamino acids, hydrogels, poly(lactic acid) or ethylenevinylacetate copolymers. In addition to being incorporated, these agents can also be used to trap the compound in microcapsules. Accordingly, the composition of the present invention may be delivered via various routes and to various sites in a mammal body to achieve a particular effect (see, e.g., Rosenfeld et al., 1991; Rosenfeld et al., 1991a; Jaffe et al., supra; Berkner, supra). One skilled in the art will recognize that although more than one route can be used for administration, a particular route can provide a more immediate and more effective reaction than another route. In some embodiments, the composition described above is administered to the subject by Attorney Docket No.206161-0065-00WO subretinal injection. In other embodiments, the composition is administered by intravitreal injection. Other forms of administration that may be useful in the methods described herein include, but are not limited to, direct delivery to a desired organ (e.g., the eye), oral, inhalation, intranasal, intratracheal, intravenous, intramuscular, subcutaneous, intradermal, and other parental routes of administration. Additionally, routes of administration may be combined, if desired. In another embodiments, route of administration is subretinal injection or intravitreal injection. The active ingredients of the present invention can be provided in unit dosage form wherein each dosage unit, e.g., a teaspoonful, tablet, solution, or suppository, contains a predetermined amount of the composition, alone or in appropriate combination with other active agents. The term “unit dosage form” as used herein refers to physically discrete units suitable as unitary dosages for human and mammal subjects, each unit containing a predetermined quantity of the compositions of the present invention, alone or in combination with other active agents, calculated in an amount sufficient to produce the desired effect, in association with a pharmaceutically acceptable diluent, carrier, or vehicle, where appropriate. The specifications for the unit dosage forms of the present invention depend on the particular effect to be achieved and the particular pharmacodynamics associated with the composition in the particular host. These methods described herein are by no means all-inclusive, and further methods to suit the specific application will be apparent to the ordinary skilled artisan. Moreover, the effective amount of the compositions can be further approximated through analogy to compounds known to exert the desired effect. It will be understood by those of skill in the art that numerous and various modifications can be made without departing from the spirit of the present disclosure. Therefore, it should be clearly understood that the forms disclosed herein are illustrative only and are not intended to limit the scope of the present disclosure. Methods of Using Compositions The present invention is further drawn to, in part, polymers and / or compositions which can be used to elicit a therapeutic effect of any therapeutic agent disclosed herein. Thus, in some embodiments, the present invention provides a method to induce an immune response in a subject. In some embodiments, the present invention provides a method of binding a protein Attorney Docket No.206161-0065-00WO on the blood-brain barrier of a subject. In some embodiments, the present invention provides a method of delivering a therapeutic agent across the blood-brain barrier of a subject. In some embodiments, the polymers and / or compositions of the present invention serve as the therapeutic agent which is being delivered across the blood-brain barrier of a subject. In some embodiments, the present invention provides a method for eliciting a therapeutic effect of a therapeutic agent, comprising administering to a subject in need thereof a composition comprising a therapeutic agent and a carbohydrate-polymer conjugate comprising a structure of Formula (I), wherein the composition delivers the therapeutic agent across the blood brain barrier. In some embodiments, the compound or composition binds to a protein which participates in the progression of a disease. In some embodiments, the compound or composition binds to a protein which allows for uptake or transport of the compound or composition across the blood brain barrier. In some embodiments, the present invention provides a method of treating or preventing a disease or disorder, for example a neurological disease or disorder, by administering the compound or composition described herein which crosses the blood brain barrier. In some embodiments, the method comprises locally delivering the composition to a neuronal population that is responsive to the relevant therapeutic agent. In some embodiments, the method modulates neurite outgrowth, neurotransmitter turnover, synapse formation, and phenotypic differentiation of neurons of the central nervous system (CNS). In some embodiments, the method is used in subjects or patients having central nervous system (CNS) disorders characterized by neuronal death, degeneration and / or dysfunction. In some embodiments, the CNS disorder is a chronic disorder. Thus, in some embodiments, the therapeutic effect is treating a CNS disorder selected from the group consisting of depression, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, stroke, head trauma, spinal cord injury, multiple sclerosis, dementia with Lewy Bodies, retinal degeneration, epilepsy, psychiatric disorders, disorders of hormonal balance, and cochlear degeneration. Therefore, in certain aspects, the present invention provides a method comprising administering the compound or composition to a subject having, or at risk for having a CNS disorder such as depression, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, stroke, head Attorney Docket No.206161-0065-00WO trauma, spinal cord injury, multiple sclerosis, dementia with Lewy Bodies, retinal degeneration, epilepsy, psychiatric disorders, disorders of hormonal balance, cochlear degeneration, and the like. In some embodiments, the method is used in patients or subjects having a tumor or cancer of the CNS. For example, in certain aspects, the method provides delivery of an anti- cancer therapeutic agent across the blood brain barrier thereby treating the patient or subject having a tumor or cancer of the CNS. In certain instances, the method induces tumor cell death, inhibits tumor migration, inhibits tumor growth, inhibits tumor proliferation, and / or inhibits tumor metastasis. Exemplary tumors or cancers of the CNS include, but are not limited to, primary CNS tumors, such as astrocytomas, glioblastomas, oligodendrogliomas, ependymomas, meningiomas, schwannomas, pituitary tumors, and lymphomas, and secondary CNS and metastatic tumors that have metastasized to the CNS from tumors originating outside of the CNS. In some aspects, the invention provides methods for treating a patient diagnosed as having a CNS disorder in its early stages, preferably prior to clinical presentation. In some aspects, the invention provides prophylactic methods for treating a patient at risk for a CNS disorder. In some aspects, the invention provides locally deliverable pharmaceutical compositions useful for treating a CNS disorder characterized by the death and / or dysfunction of a CNS neuronal population. In some embodiments, the compound or composition binds to a protein or agent at C3 of the carbohydrate. In some embodiments, the compound or composition binds to a protein or agent at C4 of the carbohydrate. In some embodiments, the compound or composition binds to a protein or agent at C3 and C4 of the carbohydrate. In some embodiments, the compound or composition binds to a protein or agent at any hydroxyl group of the carbohydrate. In some embodiments, the composition binds to a protein. In some embodiments, the composition binds to a membrane protein. In some embodiments, the composition readily crosses the blood-brain barrier. In some embodiments, the composition binds to a glucose transporter. In some embodiments, the composition binds to GLUT-1, GLUT-2, GLUT-3, and combinations thereof. In some embodiments, the composition binds to GLUT-1. Any therapeutic agent or any combination of therapeutic agents disclosed herein may be administered to a subject to treat a disease or disorder. The therapeutic agents herein can Attorney Docket No.206161-0065-00WO be formulated in any number of ways, often according to various known formulations in the art or as disclosed or referenced herein. In certain embodiments, the method of treating a disease or disorder comprises a “triggered” functionality. In other words, the system may remain inert in the body until specifically triggered. In some embodiments, the polymer is used advantageously in therapeutic applications such as to first target the polymer to a specified location, and then trigger them into an activated state. Sometimes referred to as a “dual targeted delivery system,” this feature may minimize the side effects of systemic therapeutic agents. For example, in some embodiments, upon delivering the polymer to a specific cell, a reagent, such as water, proton, acid, or protonated water, may be applied to the cell thereby causing the release of a therapeutic agent from the polymer. In some embodiments, this may provide a clinician the ability to control and visualize drug therapy noninvasively. In some embodiments, the size (e.g., average diameter of a polymer assembly) of the compound or composition of the present invention allows for passive diffusion into cells. In some embodiments, where the compound or composition is on a smaller scale, the small size (e.g., average diameter of a polymer assembly) allows the compound or compositions to travel almost anywhere in the body where therapy may need to be performed. For example, in some embodiments, the method comprises compounds that act as a hydrolysis triggered therapeutic agent delivery and therapeutic agent release systems. In various aspects, the compound or composition of the present invention can be used alone or in combination with a therapeutic agent to deliver a therapeutic agent payload to a target cell. Often, the therapeutic agent may be released based on the degradation of, e.g., a controlled release biodegradable matrix and / or polymer. The preferred dosage of the compound or nanoparticle will vary according to a number of factors, such as the administration route, the age, weight and species of the subject, but in general containing in the order of from 1 μmol / kg to 1 mmol / kg bodyweight of the compound or nanoparticle. Administration may be topical, parenteral (e.g., intravenously, intraarterially, intramuscularly, interstitially, subcutaneously, transdermally, or intrasternally), or into an externally voiding body cavity (e.g., the gastrointestinal tract, rectum, bladder, uterus, vagina, Attorney Docket No.206161-0065-00WO nose, ears or lungs), peritoneally, orally, intradermal, ocular, in an animate human or non- human (e.g., mammalian, reptilian or avian) body. In certain embodiments, the compound or composition herein is used in conjunction with an anti-cancer agent known in the art. Exemplary anti-cancer agents include, but are not limited to, immunotherapy agents, immunomodulatory agents, antineoplastic agents, chemotherapeutic agents, radioimmunotherapy agents, and monoclonal antibodies. In some embodiments, the invention provides methods of treating cancers of the brain and for the delivery of therapeutic agents and / or chemotherapeutic agents across the blood brain barrier. In some embodiments, the anti-cancer agent may be a prodrug form of an anti- cancer agent. As used herein, the term “prodrug form” and its derivatives is used to refer to a drug that has been chemically modified to add and / or remove one or more substituents in such a manner that, upon introduction of the prodrug form into a subject, such a modification may be reversed by naturally occurring processes, thus reproducing the drug. The use of a prodrug form of an anti-cancer agent in the compositions, among other things, may increase the concentration of the anti-cancer agent in the compositions of the present disclosure. In certain embodiments, an anti-cancer agent may be chemically modified with an alkyl or acyl group or some form of lipid. The selection of such a chemical modification, including the substituent(s) to add and / or remove to create the prodrug, may depend upon a number of factors including, but not limited to, the particular drug and the desired properties of the prodrug. One of ordinary skill in the art, with the benefit of this disclosure, will recognize suitable chemical modifications. Methods of Making The present invention is further drawn to, in part, a method of synthesizing a carbohydrate-polymer conjugate using ring-opening metathesis polymerization (ROMP), comprising the steps of: providing a monomer; polymerizing the monomer using a ROMP catalyst; and isolating the carbohydrate-polymer conjugate; wherein the monomer is represented by Formula (I): (I) Attorney Docket No.206161-0065-00WO wherein: R represents a substituent on ring A selected from the group consisting of hydrogen, halide, hydroxy, C1-C30 alkyl, C1-C30 alkyl halide, C1-C30 alkoxy, and any combination thereof; and L represents a divalent organic linker, wherein the carbohydrate- polymer conjugate binds to a protein located on the blood-brain barrier. In some embodiments, ring A is represented by one of the following structures: wherein O, S, NR1, or CR2R3; wherein R1, R2, and R3each independently represent a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30 alkyl, C1-C30 alkyl halide, C1-C30 alkoxy, and any combination thereof; and wherein each structure is independently optionally further substituted. In some embodiments, polymerization is performed with a target degree of polymerization. In some embodiments, the degree of polymerization is about 10 to about 500. In some embodiments, the degree of polymerization is about 20 to about 500. In some embodiments, the degree of polymerization is about 30 to about 500. In some embodiments, the degree of polymerization is about 40 to about 500. In some embodiments, the degree of polymerization is about 50 to about 500. In some embodiments, the degree of polymerization is about 60 to about 500. In some embodiments, the degree of polymerization is about 70 to about 500. In some embodiments, the degree of polymerization is about 80 to about 500. In some embodiments, the degree of polymerization is about 90 to about 500. In some embodiments, the degree of polymerization is about 100 to about 500. In some embodiments, the degree of polymerization is about 10 to about 400. In some embodiments, the degree of polymerization is about 20 to about 400. In some embodiments, the degree of polymerization is about 30 to about 400. In some embodiments, the degree of polymerization is about 40 to about 400. In some embodiments, the degree of polymerization is about 50 to about 400. In some embodiments, the degree of polymerization is about 60 to about 400. In some embodiments, the degree of polymerization is about 70 to about 400. In some embodiments, the degree of polymerization is about 80 to about 400. In some embodiments, the degree of polymerization is about 90 to about 400. In some embodiments, the degree of polymerization is about 100 to about 400. In some Attorney Docket No.206161-0065-00WO embodiments, the degree of polymerization is about 10 to about 300. In some embodiments, the degree of polymerization is about 20 to about 300. In some embodiments, the degree of polymerization is about 30 to about 300. In some embodiments, the degree of polymerization is about 40 to about 300. In some embodiments, the degree of polymerization is about 50 to about 300. In some embodiments, the degree of polymerization is about 60 to about 300. In some embodiments, the degree of polymerization is about 70 to about 300. In some embodiments, the degree of polymerization is about 80 to about 300. In some embodiments, the degree of polymerization is about 90 to about 300. In some embodiments, the degree of polymerization is about 100 to about 300. In some embodiments, the degree of polymerization is about 50 to about 250. In some embodiments, the degree of polymerization is about 60 to about 250. In some embodiments, the degree of polymerization is about 70 to about 250. In some embodiments, the degree of polymerization is about 80 to about 250. In some embodiments, the degree of polymerization is about 90 to about 250. In some embodiments, the degree of polymerization is about 100 to about 250. In some embodiments, the degree of polymerization is about 10 to about 50. In some embodiments, the degree of polymerization is about 10 to about 100. In some embodiments, the degree of polymerization is about 10 to about 150. In some embodiments, the degree of polymerization is about 10 to about 200. In some embodiments, the polymerization is performed at about 25˚C to about 100˚C. In some embodiments, the polymerization is performed at about 25˚C to about 90˚C. In some embodiments, the polymerization is performed at about 25˚C to about 80˚C. In some embodiments, the polymerization is performed at about 35˚C to about 80˚C. In some embodiments, the polymerization is performed at about 45˚C to about 80˚C. In some embodiments, the polymerization is performed at about 55˚C to about 80˚C. In some embodiments, the polymerization is performed at about 60˚C to about 80˚C. In some embodiments, the polymerization is performed at about 60˚C to about 90˚C. In some embodiments, the polymerization is performed at about 60˚C to about 100˚C. In some embodiments, the ROMP catalyst comprises a transition metal. In some embodiments, the ROMP catalyst comprises a metal selected from the group consisting of titanium, molybdenum, tungsten, tantalum, rhenium, ruthenium, any oxidation state thereof, and any combination thereof. In some embodiments, the ROMP catalyst comprises a carbene. In some embodiments, the ROMP catalyst comprises a halide. In some embodiments, the ROMP Attorney Docket No.206161-0065-00WO catalyst comprises a phosphine ligand. In some embodiments, the ROMP catalyst is selected from the group consisting of first-generation Grubbs catalyst (Grubbs I), second-generation Grubbs catalyst (Grubbs II), and third-generation Grubbs catalyst (Grubbs III). In some embodiments, the ROMP catalyst is air stable. In some embodiments, the ROMP catalyst is stable to moisture. In some embodiments, the step of polymerizing the monomer using a ROMP catalyst is performed in a glove box. In some embodiments, the step of polymerizing the monomer is done in an air-free environment. In some embodiments, the step of polymerizing the monomer is done open to air. In some embodiments, the step of polymerizing the monomer further comprises the step of adding the monomer and ROMP catalyst with at least one solvent to a solution. In some embodiments, the solvent is organic. Exemplary organic solvents include, but are not limited to, acetic acid, acetone, acetonitrile, alkanes (e.g., hexanes, heptane), amyl acetate, butanol, butyl acetate, chlorobenzene, chloroform, cumene, cyclohexane, 1,2- dichloroethene, dichloromethane, diethyl ether, dimethoxyethane, dimethylacetamide, dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, ethanol, 2-ethoxyethanol, ethyl acetate, ethyl nitrate, ethyleneglycol, formic acid, hydrazine, isopropanol, methanol, methyl acetate, 2- methyl-1-butanol, 2-methyl-1-propanol, methylbutyl ketone, methylcyclohexane, methylethyl ketone, methylpyrrolidone, methyl tert-butyl ether, nitromethane, propanol, propyl acetate, sulfolane, sarcosine, tetrahydrofuran, tetralin, toluene, 1,1,2-tricholoroethane, triethylamine, urea, xylene, and any combination thereof. In some embodiments, the step of polymerizing the monomer is automated. In some embodiments, the step of polymerizing the monomer is performed on a stir plate. In some embodiments, the step of polymerizing the monomer is performed on a hot plate. In some embodiments, the step of polymerizing the monomer is performed using a heating block. In some embodiments, the polymerization step is monitored by percent conversion. In some embodiments, “percent conversion” is defined as the percentage of monomer converted to polymer. In some embodiments, the polymerization reaches full conversion of monomer to polymer after 1 minute. In some embodiments, the polymerization reaches full conversion after about 1 minute to about 5 minutes. In some embodiments, the polymerization reaches full conversion after about 5 minutes to about 10 minutes. In some embodiments, the polymerization reaches full conversion after about 10 minutes to about 30 Attorney Docket No.206161-0065-00WO minutes. In some embodiments, the polymerization reaches full conversion after about 30 minutes to about 60 minutes. In some embodiments, the polymerization reaches full conversion after about 60 minutes. In some embodiments, the polymerization is performed using two or more monomers comprising different carbohydrates. In some embodiments, the polymerization step is performed using a monomer which does not comprise a carbohydrate. In some embodiments, the polymerization step is performed on two or more monomers with a ROMP catalyst to produce a random copolymer. In some embodiments, the polymerization step is performed to produce a statistical copolymer. In some embodiments, the polymerization step is performed on two or more monomers to produce a block copolymer. In some embodiments, the polymerization step is performed on two or more monomers to produce an alternating copolymer. In some embodiments, the polymerization step is performed to produce a stereoblock copolymer. In some embodiments, the polymerization step is performed to produce a gradient copolymer. In some embodiments, a method of polymerization alternative to ROMP is used to produce a copolymer of the carbohydrate-polymer conjugate. Exemplary methods of polymerization include, but are not limited to, atom transfer free radical polymerization (ATRP), reversible addition fragmentation chain transfer (RAFT) polymerization, anionic polymerization, cationic polymerization, living polymerization, chain shuttling polymerization, free radical polymerization, and nitroxide mediated radical polymerization (NMP). In some embodiments, the carbohydrate-polymer conjugate is isolated by evaporating solvent. In some embodiments, the carbohydrate-polymer conjugate is isolated by filtration. In some embodiments, the carbohydrate-polymer conjugate is isolated by precipitation. In some embodiments, the carbohydrate-polymer conjugate is isolated using drying. In some embodiments, the carbohydrate-polymer conjugate is isolated using dialysis. EMBODIMENTS 1. A method comprising the step of administering to a subject a composition comprising a carbohydrate-polymer conjugate comprising a structure represented by Formula (I): Attorney Docket No.206161-0065-00WO wherein: A represents a repeat unit selected from the group consisting of C5-C7alkyl, C5- C7 heteroalkyl, C5-C7 aryl, C5-C7 heteroaryl, and C5-C7 cycloalkyl; n represents an integer from 2-500; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate; and wherein the carbohydrate-polymer conjugate crosses the blood-brain barrier. 2. The method of embodiment 1, wherein the composition further comprises a therapeutic agent. 3. The method of embodiment 2, wherein the therapeutic agent is selected from the group consisting of a small molecule, an anticancer agent, an antibody, an immunomodulatory agent, a chelating agent, an imaging agent, and combinations thereof. 4. The method of embodiment 2 or 3, wherein the composition delivers the therapeutic agent across the blood brain barrier of the subject. 5. The method of any one of embodiments 1-4, wherein the composition binds to a glucose transporter. Attorney Docket No.206161-0065-00WO 6. The method of any one of embodiments 1-5, wherein the composition binds to GLUT-1. 7. The method of any one of embodiments 1-6, wherein A comprises one of the following structures: wherein: the wave line represents a bond to L; X represents O, S, NR1, or CR2R3; R1, R2, and R3each independently represent a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30 alkyl, C1-C30 alkyl halide, C1-C30 alkoxy, and any combination thereof; and each structure is independently optionally further substituted. 8. The method of any one of embodiments 1-7, wherein L comprises a C1-C30alkyl which is optionally further substituted. 9. The method of any one of embodiments 1-8, wherein L is represented by one of the following structures:

[0004] Attorney Docket No.206161-0065-00WO the wavy line represents a bond to A; * represents a bond to the carbohydrate; and R’ represents a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30alkyl, C1-C30alkyl halide, C1-C30alkoxy, and any combination thereof. 10. The method of any one of embodiments 1-9, wherein the carbohydrate is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, and any combination thereof. 11. The method of any one of embodiments 1-10, wherein the carbohydrate is selected from the group consisting of glucose, mannose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, and any stereochemical isomer thereof. Attorney Docket No.206161-0065-00WO 12. The method of any one of embodiments 1-11, wherein the carbohydrate is glucose. 13. The method of any one of embodiments 1-12, wherein the carbohydrate-polymer conjugate is a copolymer comprising a repeating unit of at least two monomers, wherein at least one monomer comprises glucose. 14. The method of any one of embodiments 1-13, wherein L forms a direct bond to the C1-, C3-, or C6-hydroxyl group of the carbohydrate. 15. The method of any one of embodiments 1-14, wherein n is between 2 and 100. 16. The method of any one of embodiments 1-15, wherein the carbohydrate-polymer conjugate comprises the following structure: . 17. The method of any one of embodiments 1-16, wherein the carbohydrate-polymer conjugate comprises the following structure: . Attorney Docket No.206161-0065-00WO 18. A method for eliciting a therapeutic effect of a therapeutic agent, comprising administering to a subject in need thereof a composition comprising a therapeutic agent and a carbohydrate-polymer conjugate comprising a structure represented by Formula (I): wherein: A represents a repeat unit selected from the group consisting of C5-C7 alkyl, C5- C7 heteroalkyl, C5-C7 aryl, C5-C7 heteroaryl, and C5-C7 cycloalkyl; n represents an integer from 2-500; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate; and wherein the composition delivers the therapeutic agent across the blood brain barrier. 19. The method of embodiment 18, wherein the subject has a central nervous system disorder selected from the group consisting of depression, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, stroke, head trauma, spinal cord injury, multiple sclerosis, dementia with Lewy Bodies, retinal degeneration, epilepsy, psychiatric disorders, disorders of hormonal balance, and cochlear degeneration. 20. The method of embodiment 18 or 19, wherein the subject has a tumor of the central nervous system (CNS) selected from the group consisting of astrocytomas, glioblastomas, Attorney Docket No.206161-0065-00WO oligodendrogliomas, ependymomas, meningiomas, schwannomas, pituitary tumors, lymphomas, and secondary CNS tumors. 21. A carbohydrate-polymer conjugate comprising a structure represented by Formula (I): wherein: A represents a repeat unit selected from the group consisting of C5-C7 alkyl, C5-C7 heteroalkyl, C5-C7 aryl, C5-C7 heteroaryl, and C5-C7 cycloalkyl; n represents an integer from 2-9; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate. 22. A composition comprising the carbohydrate-polymer conjugate of embodiment 21, further comprising a therapeutic agent. 23. The composition of embodiment 22, wherein the therapeutic agent is selected from the group consisting of a small molecule, an anticancer agent, an antibody, an immunomodulatory agent, a chelating agent, an imaging agent, and combinations thereof. 24. The composition of embodiment 22 or 23, wherein the composition delivers the therapeutic agent across the blood brain barrier of a subject. Attorney Docket No.206161-0065-00WO 25. The composition of any one of embodiments 22-24, wherein the composition binds to a glucose transporter. 26. The composition of any one of embodiments 22-25, wherein the composition binds to GLUT-1. 27. The composition of any one of embodiments 22-26, wherein A comprises one of the following structures: wherein the X represents O, S, NR1, or CR2R3; R1, R2, and R3each independently represent a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30 alkyl, C1-C30 alkyl halide, C1-C30 alkoxy, and any combination thereof; and each structure is independently optionally further substituted. 28. The composition of any one of embodiments 22-27, wherein L comprises a C1-C30alkyl which is optionally further substituted. 29. The composition of any one of embodiments 22-28, wherein L is represented by one of the following structures: Attorney Docket No.206161-0065-00WO the wavy line represents a bond to A; * represents a bond to the carbohydrate; and R’ represents a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30alkyl, C1-C30alkyl halide, C1-C30alkoxy, and any combination thereof. 30. The composition of any one of embodiments 22-29, wherein the carbohydrate is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, and any combination thereof. 31. The composition of any one of embodiments 22-30, wherein the carbohydrate is selected from the group consisting of glucose, mannose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, and any stereochemical isomer thereof. Attorney Docket No.206161-0065-00WO 32. The composition of any one of embodiments 22-31, wherein the carbohydrate is glucose. 33. The composition of any one of embodiments 22-32, wherein the carbohydrate-polymer conjugate is a copolymer comprising a repeating unit of at least two monomers, wherein at least one monomer comprises glucose. 34. The composition of any one of embodiments 22-33, wherein L forms a direct bond to the C1-, C3-, or C6-hydroxyl group of the carbohydrate. 35. The composition of any one of embodiments 22-34, wherein n is between 2 and 100. 36. The composition of any one of embodiments 22-35, wherein the carbohydrate-polymer conjugate comprises the following structure: . 37. The composition of any one of embodiments 22-36, wherein the carbohydrate-polymer conjugate comprises the following structure: . Attorney Docket No.206161-0065-00WO 38. A method for eliciting a therapeutic effect of a therapeutic agent, comprising administering to a subject in need thereof a composition comprising a therapeutic agent and the carbohydrate-polymer conjugate of embodiment 21. 39. The method of embodiment 38, wherein the subject has a central nervous system disorder selected from the group consisting of depression, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, stroke, head trauma, spinal cord injury, multiple sclerosis, dementia with Lewy Bodies, retinal degeneration, epilepsy, psychiatric disorders, disorders of hormonal balance, and cochlear degeneration. 40. The method of embodiment 38 or 39, wherein the subject has a tumor of the central nervous system (CNS) selected from the group consisting of astrocytomas, glioblastomas, oligodendrogliomas, ependymomas, meningiomas, schwannomas, pituitary tumors, lymphomas, and secondary CNS tumors. EXPERIMENTAL EXAMPLES The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the present invention and practice the claimed methods. The following working examples therefore are not to be construed as limiting in any way the remainder of the disclosure. Example 1: Elucidating the Relationship Between Glycan Macromolecular Structure, Recognition, and Anticancer Function The present invention is drawn to, in part, carbohydrate-polymer conjugates (CPCs) with unambiguous local chemical composition and well-defined global structure for use Attorney Docket No.206161-0065-00WO as tools to understand the nature of multivalent carbohydrate recognition. The mechanisms governing how the hierarchical arrangement of glycans potentiates their recognition by human lectins remain incomplete. Initial investigations were performed on the binding of β- galactosides to Galectin-3 (Gal-3), a protein with vital roles in myriad diseases, including cancer. β-galactose and lactose were derivatized with norbornenyl moieties to afford protecting- group-free glycomonomers. Using direct, graft-through ring opening metathesis polymerization (ROMP), a suite of CPCs was generated and systematically evaluated for their ability to bind to Gal-3. Significantly, galactose-based CPCs (Gal-CPCs) showed a ~3600-fold improvement in Gal-3 binding over the monosaccharide ligand. Moreover, complete grafting density was required for maximal binding to Gal-3, with Gal-CPCs displaying more than a 350% enhancement in binding to Gal-3 over copolymers at 50% galactose density. Coarse-grain models suggest that this arises from reduced carbohydrate-carbohydrate interactions and enhanced solvent accessibility in fully grafted CPCs. This translates to significant differences in the function of these materials as Gal-3 inhibitors in in vitro models of 4T1 triple-negative breast cancer. Gal-CPCs inhibited the migration by greater than 60% relative to vehicle controls and significantly outperformed all other treatment groups. Together, these findings shed light on how the macromolecular structure of carbohydrates dictates their ability to bind human lectins and paves the way to the development of polymeric cancer therapeutics comprised of simple, inexpensive β-galactosides. To elucidate the mechanisms underlying carbohydrate recognition by mammalian lectins, glycopolymer probes were developed with precise local chemical composition and well-defined global macromolecular structure. It was reasoned that the graft- through ring opening metathesis polymerization (ROMP) of unprotected carbohydrates would afford well-defined glycopolymers with maximal grafting density and unambiguous local chemical structure (i.e., each sidechain is functionalized, and no post-polymerization manipulations are required). ROMP is ideal in this regard, as it is a controlled polymerization method (Bandlow et al., 2017, J. Am. Chem. Soc., 139, 16389) that allows for the generation of polymers with low dispersity and high reproducibility. Its initiators (Xiong et al., 2013, Nature, 497, 392) display excellent functional group tolerance, which permits the incorporation of a diverse array of functionalized monomers, such as the dense concentration of hydroxyl moieties on carbohydrates (Kanai et al., 1997, J. Am. Chem. Soc., 119, 9931; Mortell et al., 1994, J. Am. Attorney Docket No.206161-0065-00WO Chem. Soc., 116, 12053; Tang et al., 2016, ACS Macro Lett., 5, 413; Fraser et al., 1995, Macromolecules, 28, 7248). Moreover, the rigid, sp2-hybridized backbones of poly(norbornene) are akin to the polypeptide backbones on which oligosaccharides are natively displayed. As a model system, the binding of β-galactosides by galectin-3 (Gal-3), a protein involved in myriad physiological processes (Joeh et al., 2020, Proc. Natl. Acad. Sci., 117, 27329) and in the progression of multiple diseases (Califice et al., 2004, Int. J. Oncol., 25, 983; Feilchenfeldt et al., 2003, Modern Pathology, 16, 1117; Gao et al., 2013, Respiratory Research, 14, 136), including cancer, was studied. As such, understanding the nature of its carbohydrate recognition would have wide-ranging biomedical implications (Farhadi et al., 2021, Proc. Natl. Acad. Sci. USA, 118; Pradmudya, 2019, Biomaterials Science, 7, 4848). Like other galectin family members, Gal-3 recognizes and binds β-galactosides in a multivalent fashion (Restuccia et al., 2018, ACS Biomat. Sci. Eng., 4, 3451; Laaf et al., 2017, Bioconjugate Chemistry, 28, 2832). Gal-3 is overexpressed in many cancers, where it inhibits immune cell action in the tumor microenvironment (Guo et al., 2020, Oncol. Rep., 44, 1799), contributes to cell proliferation (Paron et al., 2003, Biochem. Biophys. Res. Commun., 302, 545; Preillo et al., 1998, J. Mol. Med., 76, 402), and promotes cancer cell migration (Liu, 2005, Nat. Rev. Cancer, 5, 29). Previous research on targeting Gal-3 has focused on synthetically laborious small molecule inhibitors (Giguere et al., 2006, Chem. Comm., 22, 2379; Zetterberg et al., 2022, J. Med. Chem., 65, 12626). Of note is TD139, a small molecule thiodigalactoside against Gal-3 is currently undergoing clinical trials for idiopathic pulmonary fibrosis (Nikhil et al., 2021, Eur. Resp. J., 57, 2002559). While there are two reports on polymers designed to bind to Gal-3, neither have achieved more than a ~16% grafting density (Filipova et al., 2020, Biomacromolecules, 21, 3122; Vrbata et al., 2022, J. Med. Chem., 65, 3866) and utilize post- polymerization modification methods. Moreover, these reports focus on therapeutic development, with little insight on a fundamental understanding of the interactions between Gal- 3 and multivalent ligands. Given these facts, it was reasoned that understanding the macromolecular nature of Gal-3 binding to β-galactosides could both offer fundamental insights into carbohydrate recognition and provide a potential pathway to the development of new polymeric materials for cancer therapy. Herein, carbohydrate-polymer conjugates (CPCs) have been synthesized via the direct, graft-through polymerization of two β-galactoside ligands for Gal-3. These materials Attorney Docket No.206161-0065-00WO were used to evaluate how carbohydrate multivalency and density influences lectin recognition and therapeutic function. It was found that the multivalent display of carbohydrates overrides differences in both individual ligand affinities and overall degree of polymerization. Moreover, complete grafting density is required for maximal binding to Gal-3. Coarse-grain analyses offer mechanistic insight into the nature of these interactions, indicating that fully grafted CPCs outperformed others due to their highest solvent-accessible surface area and reduced carbohydrate-carbohydrate interactions. Significantly, these differences translate into distinct actions of CPCs as galectin-3 inhibitors in in vitro models of triple-negative breast cancer. Fully grafted CPCs inhibit the migration of 4T1 cells by over 60% compared to vehicle controls. Together, these findings provide insight on how the macromolecular density of carbohydrates modulates their recognition by proteins and can guide the design of multivalent galectin- targeting materials for applications in cancer and beyond. Glycomonomer Design To probe the effect of multivalency on the binding of β-galactosides to Gal-3, β- galactose and lactose were chosen as model ligands as they are the simplest naturally occurring glycans recognized by Gal-3 (Nio-Kobayashi, 2021, Front. Neuroanat., 15) and have vastly different affinities for the lectin (~150 mM for galactose, 200 µM for lactose) (Saraboji et al., 2012, Biochemistry, 51, 296). Moreover, previous reports have found that longer linkers on polymer sidechains increase self-aggregation from intramolecular hydrophobic and hydrogen bonding (Mosquera-Giraldo et al., 2016, Biomacromol., 17, 3659). Therefore, it was hypothesized that β-galactosides bound by a shorter linker would exhibit improved binding potency over those with longer linkers. Thus, both galactose and lactose were derivatized with norbornenyl handles with variations in the spacing between carbohydrate ligand and polymerizable moiety. With these design considerations in mind, two glycomonomers were synthesized from galactose (mono-Gal7and mono-Gal10) and two glycomonomers were synthesized from lactose (mono-Lac7and mono-Lac10) with 7 and 10 atoms between glycan epitope and norbornenyl handle, respectively (Fig.1A). Briefly, a norbornenyl moiety was appended with an amino acid, followed by addition of an amino alcohol using standard amidation conditions. The linker was formed using two components so that an amide could be incorporated, as it was Attorney Docket No.206161-0065-00WO hypothesized that a purely hydrocarbon-based linker may overwhelm the hydrophilicity of the carbohydrate and reduce solubility. Moreover, an amide linker provides hydrogen-bonding capability and a way to rapidly change the linker length. Lastly, the norbornenyl-linker conjugate was conjugated with a commercially available acetylated sugar to generate a protected glycomonomer that, following deprotection, yields the final glycomonomer with a native glycosidic bond, which was hypothesized to play a role in the recognition of the carbohydrate by Gal-3. Carbohydrate-Polymer Conjugate (CPC) Synthesis and Analysis. With glycomonomers in hand, each was subjected to ROMP using Grubb’s III generation catalyst in dry DMF at 60ºC to afford CPCs (Fig. 1B). Altogether, a suite of 12 total CPCs from galactose (Gal-CPC) and lactose (Lac-CPC) with variations in linker length (7 or 10 atoms) and target degree of polymerization (50, 100, or 250) was synthesized. An attempt was made to monitor the polymerization progress of mono-Gal7 by1H-NMR, but complete conversion occurred in less than 5 minutes (Fig. 1C). Likewise, all other glycomonomers were also efficiently converted to CPCs within the same timeframe (Fig. 2). Following polymerization, all CPCs were characterized using size exclusion chromatography with multi- angle light scattering (SEC-MALS) to determine the degree of polymerization (DP) and dispersity (Đ) (Table 1, Fig. 3). Table 1. Polymer Characterization by SEC-MALS. DP calculated from the initial monomer-to-initiator ratio ([M]0 / [I]0) for each polymer, and all Đ Attorney Docket No.206161-0065-00WO were below 1.25. This suggests a controlled polymerization process with narrow molecular weight distributions and afforded well-defined CPCs for use in future analyses. Galectin-3 Binding as a Function of Valency, Linker, and Glycan Identity. The ability of all CPCs to be recognized by Galectin-3 were investigated in vitro. For these analyses, microscale thermophoresis (MST) was utilized, as it is a fully solution-based technique that measures the motion of fluorescent molecules in response to a microscopic temperature gradient (Bandlow et al., 2017, J. Am. Chem. Soc., 139, 16389; Xiong et al., 2013, Nature, 497, 392). It was posited that this technique would more accurately recapitulate the natural interactions between the lectin and glycopolymer than would be obtainable by immobilization-based techniques (e.g., surface plasmon resonance). With this in mind, the fluorophore Atto 488 was conjugated to Gal-3 at its C-terminal domain so that the movement of the protein could be tracked without interfering with its β-galactoside binding site (Sorme et al., 2005, J. Am. Chem. Soc., 127, 1737). The suite of CPCs was then incubated with the tagged protein at increasing polymer concentrations and analyzed their interactions to determine their dissociation constants (Kd) as a function of β-galactoside identity, linker length, and overall degree of polymerization (Table 2). Table 2. MST Analysis of Galectin-3 Binding by CPCs. β-galactose on a polymer scaffold (i.e., Gal-CPCs) provides multivalent materials capable of binding Gal-3 with an apparent Kd in the mid-micromolar range. The most effective CPC exhibited approximately a Attorney Docket No.206161-0065-00WO 3600-fold improvement compared to monomeric β-galactose. This finding is consistent with observations in other glycomacromolecule systems (Cervin et al., 2020, ACS Infect. Dis., 6, 1192; Gonnot et al., 2023, Biomacromolecules, 24, 3689), where multivalency enhances potency in a non-linear manner, a phenomenon termed "avidity" (Zumbro et al., 2019, Biophys. J., 117, 892). Interestingly, there is a diminishing return on avidity as the degree of polymerization (DP) is increased. Gal-CPCs at DP=100 show approximately double the binding avidity over Gal-CPCs at DP=50; however, Gal-CPCs at DP=250 show no appreciable increase in avidity relative to DP=100. Moreover, the number of atoms linking the glycan epitope to the polymer backbone (i.e., 7 vs.10 atoms) showed no effect on Kd. When comparing Gal-CPCs to Lac-CPCs, unintuitive binding behavior was observed. Lac-CPCs were able to bind Gal-3 with higher avidity than Gal-CPCs at all DPs evaluated; however, the increase was marginal. This was unexpected, considering the vast differences in individual ligand affinities between galactose (~150 mM) and lactose (200 µM). Thus, it was concluded that the recognition of β-galactosides in this system is predominantly influenced by multivalency, rather than the specific identity of individual ligands. This observation may elucidate why Gal-3 exhibits the ability to bind various multivalent galactosides found in nature and why the most specific natural Gal-3 ligand remains unknown. Galectin-3 Binding as a Function of Glycan Epitope Density. Motivated by the findings, the effect of multivalency on glycan recognition by Gal-3 was further investigated. Specifically, the impact of sugar epitope density on binding avidity was studied, considering previous findings indicating the significance of both density and valency in lectin binding (Qin et al., 2016, Biomaterials, 101, 189). Towards this end, a “diluent” monomer was synthesized, which contained a single hydroxyl moiety (mono-OH7) in place of the glycan epitope (Fig.4). Copolymers were synthesized together with mono-Gal7 using ROMP at 1:1 and 5:1 ratios of diluent:galactose, respectively, to mimic a graft-to polymer at 50% and 20% grafting density (Fig.5A, Table 3, Table 4). Table 3. SEC-MALS data for polymers used in MST experiments. Entry Glycan Linker Target Theo. MnMwDP*Ð length DP Mn(kDa) (kDa) (kDa) Attorney Docket No.206161-0065-00WO 4 Galactose 7 50 22.7 22.5 23.5 49 1.04 5 Galactose 7 100 45.4 45.7 49.3 101 1.08 6 Galactose 7 250 113.6 110.8 176.8 244 1.60 7 Galactose 10 50 24.8 21.2 21.7 43 1.02 8 Galactose 10 100 49.7 46.3 48.7 93 1.05 9 Galactose 10 250 124.1 93.8 116.9 189 1.25 10 Lactose 10 50 32.9 29.6 35.1 45 1.18 11 Lactose 10 100 65.9 73.2 93.5 111 1.28 12 Lactose 10 250 164.7 119.6 193.7 182 1.62 13 Gal (50), OH 10, 7 100 39.4**47.5 75.9 120**1.60 (50) 14 Gal (50), OH 10, 7 250 83.3**62.0 85.1 186**1.37 (200) *DP calculated as Mn / MWmonomer**MWmonomercalculated as weighted average based on target DP and grafting density Polymers in this table: Entry 4 = Gal-CPC, DP = 50, linker = 7; Entry 7 = Gal-CPC, DP = 50, linker = 10; Entry 8 = Gal-CPC, DP = 100, linker = 10; Entry 9 = Gal-CPC, DP = 250, linker = 10; Entry 10 = Lac-CPC, DP = 50, linker = 10; Entry 13 = Co-CPC-50%; Entry 14 = Co- CPC-20%. Table 4. SEC-MALS data for polymers used in biological experiments. Entry GlycanLinkerTarget Theo. MnMwlengthDP MnDP*Ð (kDa) (kDa)(kDa)18 Galactose 7 100 45.4 49.3 52.1 109 1.06 19 Lactose 7 100 61.6 60.8 63.2 99 1.04 20Gal (50), OH(50) 7, 7 100 37.3 48.7 50.8 130 1.0421Galactose, monoCy5 7 100 45.4 35.8 43.5 78 1.2222 Glucose 4 50 19.9 24.9 25.8 62 1.07 *DP calculated as Mn / MWmonomerPolymers in this table: Entry 18 = Gal-CPC, DP = 100, linker = 7; Entry 19 = Lac-CPC, DP = 100, linker = 7; Entry 20 = Co-CPC-50%. For these analyses, the theoretical DP of mono-Gal7was held at 50 and the mol ratio of mono-OH7 was varied to achieve the desired glycan composition. This yielded two copolymers: one copolymer with 50% galactose grafting density at DP = 100 (Co-CPC-50%) and one copolymer with 20% galactose grafting density at DP = 250 (Co-CPC-20%). Strikingly, the ability of the copolymers to bind Gal-3 was significantly abrogated as compared to that of Gal-CPC (Fig.5B, Table 5). Reducing the overall grafting Attorney Docket No.206161-0065-00WO density by 50% (Co-CPC-50%) reduced the binding avidity by ca. 350% relative to Gal-CPC at DP = 50, when glycan epitope number is matched. When the overall degree of polymerization is kept constant, this discrepancy becomes even more pronounced. Gal-CPCs at DP = 100 show an approximate 7-fold higher binding avidity to Gal-3 over Co-CPC-50%, and Gal-CPCs at DP = 250 show an approximate 8-fold enhancement over Co-CPC-20%. This is counter to what has been observed in other glycomacromolecule systems (Kruger et al., 2021, ACS Cent. Sci., 7, 624; Matsuoka et al., 2021, Bioorg. Med. Chem. Lett., 52, 128389; Richards et al., 2012, Angew. Chem. Int. Ed., 51, 7812; Schuster et al., 1997, J. Mol. Catal. A: Chem., 116, 209; Wilkins et al., 2018, ACS Macro Lett., 7, 1498). As such, the solution behavior of these materials was investigated using computational models. Table 5. Dissociation constants (Kd) for Gal-CPCs and copolymers. reduced the binding avidity by ca. 350% relative to Gal-CPC at DP = 50, when glycan epitope number is matched. When the overall degree of polymerization is kept constant, this discrepancy becomes even more pronounced. Gal-CPCs at DP = 100 show an approximate 7-fold higher binding avidity to Gal-3 over Co-CPC-50%, and Gal-CPCs at DP = 250 show an approximate 8-fold enhancement over Co-CPC-20%. This is counter to what has been observed in other glycomacromolecule systems, as well as the general understanding that the dense orientation of glycan ligands limits their accessibility by lectins (Naka et al., 2023, Polymer Journal, 55, 1379). As such, the solution behavior of these materials was investigated using computational models. Attorney Docket No.206161-0065-00WO Coarse-Grain Modeling Analyses. To investigate CPC conformations in solution, coarse-grained (CG) molecular dynamics (MD) simulations were employed, which enabled studying large molecular systems like bottlebrush polymers (BBPs) for several microseconds (Joshi, 2021, Molecular Simulation, 57, 786; Mohammadi et al., 2021, Comp. Mater. Sci., 199, 110720). To probe the effect of grafting density on CPC conformation, CG MD simulations were performed by simulating three types of CPCs with similar grafting densities to those used in present experiments. Here, transferable CG models of peptides (Conway et al., 2020, Mol. Syst. Des. Eng., 5, 675; Mohammadi et al., 2023, Biomacromolecules, 2, 24, 4078), hydrocarbons (An et al., 2018, J. Phys. Chem. B, 122, 7143; An et al., J. Phys. Chem. B., 123, 909), and carbohydrates were utilized to model and simulate CPCs in explicit water. CG MD simulations were carried out for three initial configurations for each system, on the Nanoscale Molecular Dynamics (NAMD) simulation package using the NPT (T=298 K) for 500 ns (Phillips et al., 2005, J. Comp. Chem., 26, 1781). Additional details regarding the mapping schemes, CG models, and simulation details are found in Table 6, Table 7, and Table 8. Table 6. Comparison of bulk properties obtained for β-galactose and β-glucose using AA and CG simulations. Property β-galactose β-glucose AA CG AA CG Density (g / cm3) 1.44 ± 0.00 1.49 ± 0.00 1.44 ± 0.00 1.48 ± 0.00 Heat of vaporization 29.65 ± 0.19 30.49 ± 0.06 30.34 ± 0.08 30.33 ± 0.03 (kcal / mol) Surface Tension 114.05 ± 35.20 135.35 ± 9.69 124.11 ± 24.92 127.75 ± 41.34 (mN / m) Gibb’s solvation-free 16.78 ± 3.16 14.57 ± 0.24 16.78 ± 2.65 14.65 ± 0.35 energy (kcal / mol) For obtaining bulk properties, systems containing 800 monosaccharide molecules in a cubic box of length 54 Å were made using Packmol (Martinez et al., 2009, J. Comp. Chem., 30, 2157) and simulated under periodic boundary conditions (Allen, Computer Simulation of Liquids, 2017) at 300 K and 1 atm in an NPT ensemble. Single monosaccharides in vacuum cubic boxes were generated and simulated under the same conditions, using an NVT ensemble. For both NPT and NVT ensembles, MD simulations were performed for 20 ns for AA and 50 ns Attorney Docket No.206161-0065-00WO for CG systems. All the AA and CG MD simulations for carbohydrates were performed by using the NAMD 2.14 program (Phillips et al., 2005, J. Comp. Chem., 27, 1781). The last 10 ns (for AA) and 20 ns (for CG) were utilized to calculate the density and heat of vaporization. Density was obtained by dividing the mass of the system by the final equilibrated volume. Theheat of vaporization was calculated using the following equation:௩^ ^ 1^ 1∆^ ^ =^ ^^^^ ^^ − ^^^^^^^ + ^^^^^ ^^^^Where and bulk phase, respectively. R is the the number of molecules. To calculate the surface tension, 40 ns (for AA) and 80 ns (for CG) MD simulations were performed, in the NVT ensemble, of monosaccharide slabs by expanding the Z-axis of the cubic cell of equilibrated NPT bulk simulations of 800 molecules to 160 Å (~3 times greater than theX and Y axis). Surface tension was calculated using the following equation:^ = ^௭4 < 2 ௭^௭ − ௫^௫ − ௬^௬ >where LZ is the the diagonal elements of the pressure tensor, and angular brackets denote an ensemble average. For obtaining Gibbs’ solvation-free energies of the monosaccharides, adaptive biasing force (ABF) MD simulations (Mohammadi et al., 2023, Biomacromolecules, 24, 4078; An et al., 2019, J. Phys. Chem. B, 123, 909) were utilized. These simulations were also conducted using the NAMD 2.14 program and the Colvars package. The ABF simulations were performed in the NVT ensemble, where temperature control was achieved in the same manner as for bulk MD simulations. The initial configurations of single monosaccharide solvated in water (TIP3P for CHARMM and GLYCAM, SPCE for OPLS-AA, and CG water beads for CG monosaccharides) were generated using Packmol (Fiorin et al., 2013, Mol. Phys., 111, 3345). The initial configuration was generated by solvating the monosaccharide in a cubic box of length 40 Å, keeping the monosaccharide in the center of the box. The solvated box contained 2000 AA water molecules and 1000 CG water beads. The air / vacuum-water interface was created by extending the z-axis to 80 Å. The monosaccharide molecule was transported from the center of the solvated box to vacuum by moving it along the z-axis at a 35 Å distance. This 35 Å is referred to as the reaction coordinate, which is a measure of the distance between the center of mass (COM) of the solvated box and that of the molecule in the Attorney Docket No.206161-0065-00WO z-direction. To enhance the efficiency of the ABF simulations for AA systems, the entire reaction coordinate was equally divided into seven consecutive windows, and 20 ns MD simulation was performed at each window. For CG systems, one 100 ns ABF MD simulation was performed. The Gibbs solvation-free energy profile was obtained along the z-axis from the COM of the box to 35 Å in the vacuum. Force-field files used to perform CG MD simulations along with the NAMD input files are provided as supplementary files and the corresponding force-field (FF) parameters are shown in Table 7. Table 7. List of all FF parameters used for this study. Bonded interaction parameters Bond Kbb0TOL4 TOL4 36.609 2.52 TOL4 C2M 50.014 2.42 C2M COO2 40.016 2.66 CON2 CCOH 38.000 3.00 C2M CON2 37.695 3.561 C2M DBC 37.695 3.561 DRO DGC 160.000 1.86 DRO FSB 160.000 1.86 DBC FSB 90.000 2.2250 DGC FSB 90.000 2.2250 DGC DBC 100.000 2.2506 DBC DBC 100.000 2.2506 DBC DBB 50.000 2.8645 DRO DBB 50.000 2.110 DBC FSB 100.000 2.00 Angle K^^0TOL4 TOL4 TOL4 15.000 144.226 TOL4 TOL4 C2M 15.000 100.000 TOL4 C2M COO2 15.000 120.000 C2M COO2 C2M 15.000 162.000 CON2 C2M DBC 15.000 162.000 CON2 C2M COO2 15.000 162.000 C2M CON2 C2M 15.000 162.000 C2M DGC DRO 16.555 124.000 DGC DGC DRO 100.000 110.000 DBC DBC DGC 100.000 110.000 DBC DBC DBB 90.000 110.000 DBC DBB DRO 100.000 110.000 Attorney Docket No.206161-0065-00WO DGC DRO DBB 80.000 110.000 FSB DRO DBB 80.000 110.000 DBC DGC FSB 100.000 110.000 DGC FSB DRO 100.000 110.000 DBB DBC FSB 100.000 123.000 FSB DBC DBC 100.000 114.000 DRO FSB DBC 100.000 115.000 DGC FSB DBC 100.000 130.000 Dihedral Kϕn ϕ0TOL4 TOL4 TOL4 TOL4 1.0 2.0 0.0 TOL4 TOL4 TOL4 C2M 1.0 2.0 60 TOL4 TOL4 C2M COO2 1.0 2.0 0.0 C2M TOL4 TOL4 C2M 1.0 2.0 0.0 DRO DBB FSB DRO 0.5 3.0 0.0 DGC DBB FSB DRO 0.5 2.0 -120.0 DBC DGC DBC DBC 1.0 1.0 53.5 DBC DBC DBC DGC 1.0 1.0 53.5 DBC DBC DGC DBB 1.0 1.0 -53.5 DGC DBB DRO FSB 1.0 1.0 -60.0 DBB DRO FSB DGC 1.0 1.0 60.0 DGC DBC DGC DSB 1.0 1.0 53.5 DRO DGC DBC DBC 1.0 1.0 53.5 Nonbonded interaction parameters Self-interactions Epsilon Rmin / 2 DGC -0.6200 1.9700 DBC -0.6200 1.9700 DBB -1.1600 2.2740 DMB -0.3710 2.4354 DSB -0.2700 1.9955 FSB -0.2700 1.9955 DRO -0.3650 1.9955 CON2 -1.1332 2.4343 COO2 -0.8714 2.3950 TOL4 -0.5839 2.6920 CCOH -0.7999 2.3741 C2M -0.3420 2.4343 W -1.1425 2.1170 Cross interactions Epsilon RminDBB - W -0.780000 4.250000 DMB - W -0.716448 4.109073 DRO - W -0.620000 4.523235 DGC - W -0.700000 4.250000 DBC - W -0.670000 4.350000 DSB - W -0.630000 4.050000 Attorney Docket No.206161-0065-00WO C2M - W -0.440000 4.235900 CON2 - W -1.095258 4.5513 CCOH - W -0.798158 4.4911 COO2 - W -1.056721 4.512 MD simulations were carried out using the NAMD simulation package for 500 ns with periodic boundary conditions. The NPT ensemble with T=298 K, and P=1 bar was used for the production run. A timestep of 10 fs was used with a cut-off of 12 Å. Visual Molecular Dynamics (VMD) software was used for visualization and analysis of trajectories (Humphrey et al., 1997, J. Molec. Graphics, 14, 33). Furthermore, to obtain more statistically significant results, each system was simulated thrice using different initial configurations (Table 8). Entire trajectories from all simulations were used to calculate the evolution of Rg and solvent accessible surface areas (SASA). However, aspect ratios, distributions and radial distribution functions (RDFs) were analyzed for the last quarter of the trajectories (150 ns), when all systems were considered to have been equilibrated (Joshi et al., 2022, Comp. Mater., 8, 45; Joshi et al., 2021, Carbon, 180, 244). Analyses were carried out using the CPPTRAJ package and in-house TCL and Python scripts (Roe, 2013, J. Chem. Theo. Comp., 9, 3084). Table 8. List of all CG MD simulations performed. System bundle Systems studied, replicas Total run time Co-CPC-50% 3 (different starting configurations; 500 ns each) 1.5 μs Gal-CPC 3 (different starting configurations; 500 ns each) 1.5 μs Lac-CPC 3 (different starting configurations; 500 ns each) 1.5 μs Visual inspection of CG MD simulations trajectories revealed that all CPCs collapsed into globular aggregates within the initial 100 ns (Fig.6A). It was observed that the monosaccharide functional groups aggregated together initially, followed by the collapse of the hydrophobic CPC backbones to reduce backbone interactions with water. This collapse of the CPC backbone was simultaneously stabilized through the increased carbohydrate aggregation, which resulted in equilibrated globular structures with aspect ratios of 0.68 ± 0.12, 0.71 ± 0.10, and 0.69 ± 0.10 for Lac-CPC, Gal-CPC, and Co-CPC-50% systems, respectively. Additionally, following equilibration, Rgvalues for Lac-CPC systems fluctuated around a mean value of 2.176 ± 0.35 nm compared to 1.771 ± 0.06 nm and 1.772 ± 0.2 nm of Gal-CPC and Co-CPC- Attorney Docket No.206161-0065-00WO 50% systems, which were much lower than the Rg values of stretched CPCs (Fig.7). Based on aspect ratios and Rgvalues for these globule-like structures, the relation Rg / Rh≈ 0.78 was utilized to estimate the hydrodynamic radii (Rh) of the present CPCs (Hsiao, 2006, Macromolecules, 39, 7125; Nygaard et al., 2017, Biophys. J., 113, 550). These values for the Lac-CPC, Gal-CPC, and Co-CPC-50% systems were 2.789 nm, 2.271 nm, and 2.272 nm, respectively. These data were in good agreement with experimental Rh values, measured via dynamic light scattering (DLS, Table 9), for Lac-CPCs (Rh= 3.35 nm), Gal-CPCs (Rh= 2.55 nm) and the statistical copolymer (Rh= 2.45 nm). Table 9. Polymer size characterized via dynamic light scattering. Polymer Size (d.nm)*Standard Deviation (d.nm)*Entry 15 5.14 0.14 Entry 16 6.77 0.74 Entry 17 4.89 0.46 Entry 18**9.22 0.34 Entry 19**8.08 0.74 Entry 20**5.31 0.25 *Calculated using percent number. **Measurement was run in 1X PBS To examine microscopic structural correlations in the system, the radial distribution functions (RDFs) were calculated between different bead types (Fig.8). RDFs between CPC backbone and water showed greater hydration of the Lac-CPC system, followed by the Gal-CPC and Co-CPC-50% systems. Similarly, RDFs between monosaccharide groups in the CPCs with water showed similar structural correlations with slightly greater hydration for the monosaccharide groups in the Lac-CPC system. RDFs between monosaccharide groups that are known to be important for binding to Gal-3 showed that the structural correlation between monosaccharide groups was highest for Co-CPC-50% systems compared to homopolymers Lac- CPC and Gal-CPC (Fig.6B). These data indicate that the homopolymer systems show more exposure of monosaccharide groups to the solvent, whereas for the Co-CPC-50% system, monosaccharide groups are more strongly aggregated. Structural correlations between water and monosaccharide groups follows the order: Lac-CPC > Gal-CPC > Co-CPC-50%. Similarly, the solvent accessible surface areas (SASA) values for all systems were calculated, showing the highest values for the Lac-CPC Attorney Docket No.206161-0065-00WO system followed by Gal-CPC and Co-CPC-50% systems (Fig.9). This could be the result of stronger aggregation between monosaccharide groups in Co-CPC-50% compared to the rest, thus further validating the RDF data. Additionally, the nonbonded energies between different groups in the systems were isolated and obtained for the entire trajectory (Fig.10). While the nonbonded energies between backbone-water and between monosaccharide groups showed similar values in all CPC systems, a clear difference was observed for energies between monosaccharide groups and water (Fig.6C). The interaction energy with water was found to be lowest with monosaccharide groups in the Gal-CPC system, indicating the most favorable interactions. This was followed by the monosaccharide groups in the Lac-CPC system, whereas the Co-CPC-50% system exhibited the most unfavorable interactions with water. These data complement prior observations indicating that monosaccharide groups in Gal-CPC and Lac- CPC systems show more favorable interactions with water, thus making them available for binding to Gal-3. Moreover, these data are supported experimentally via dynamic light scattering (DLS, Fig.11), with Lac-CPCs having the largest hydrodynamic diameter (6.7 nm), followed by Gal-CPCs (5.1 nm) and finally the statistical copolymer (4.9 nm). Cellular Uptake and Cytotoxicity of CPCs. To evaluate whether differences in binding avidity and solution behavior also translates to differences in biological function, the ability of CPCs to be taken up by cells was first evaluated. As a model system, Gal-CPCs containing a near infrared (NIR) fluorophore (Proetto et al., 2018, ACS Cent. Sci., 4, 1477) were synthesized (Fig.12) and their uptake by 4T1 triple negative breast cancer cells was evaluated. Gal-CPCs were efficiently taken up by cells (Fig.13A) and appear to localize around the exterior of the nucleus. It was then confirmed that all CPCs were not acutely cytotoxic in both a Gal-3-negative cell line (LNCaP) and a Gal- 3-positive cell line (4T1), as confirmed by Western Blot (Fig.14). No system showed evidence of cytotoxicity after 4 h incubation at polymer concentrations of 10 µM (Fig.13B and Fig. 13C). In vitro Anticancer Activity as a Function of Glycan Display. Among its multiple tumorigenic activities, intracellular Gal-3 is known to promote both cancer cell proliferation and migration. As such, it was important to understand Attorney Docket No.206161-0065-00WO whether CPCs could inhibit cell proliferation and migration, and whether the differences in in vitro binding avidity translates to appreciable differences in biological activity. To assess the effect of structure on Gal-3-promoted cell proliferation, both 4T1 cells and LNCaP cells were incubated with Gal-CPCs (DP = 100), Lac-CPCs (DP = 100), or Co-CPC-50% at 10 µM with respect to polymer. As a control, cells were incubated with galactose at 100 µM. The effect of treatment on cell proliferation was evaluated by comparing the cell viability of 4T1 cells to those of LNCaP cells after 24 h incubation. As expected, no effect on LNCaP cell proliferation was observed in any system. However, Gal-CPCs significantly inhibited proliferation of 4T1 cells compared to LNCaP cells (Fig.13D) by approximately 20%, suppressing the growth of cancer cells in a galectin-3-dependent manner. Conversely, Co-CPC-50% was unable to significantly suppress proliferation, indicating that full grafting density is necessary for optimal biological function. It was noted that Lac-CPCs trend towards being antiproliferative, but Gal-CPCs outperformed these materials. This discrepancy was attributed to the fact that lactose is comprised of galactose bound to glucose by a β-1,4-glycosidic linkage. As such, incubation of Lac-CPCs with cancer cells may inadvertently liberate glucose when in the biological milieu, which has been seen to promote cell growth in glucose-based CPCs (Fig.14). This underscores the importance of considering both glycan composition, as well as presentation, when designing carbohydrate-based therapeutics. As a final analysis of the effect of glycan macromolecular structure on biological function, the ability of the materials to inhibit cancer cell migration was evaluated. The MAPK / ERK signaling pathway plays a crucial role in cancer cell motility, contributing to the invasive metastatic phenotype of cancer cells. Given the involvement of Gal-3 in the MAPK / ERK signaling pathway and influence on cancer cell motility (Vrbata et al., 2022, J. Med. Chem., 65, 3866), the ability of these materials to inhibit the migration of 4T1 cells was evaluated. A wound-healing (scratch) assay (Liang et al., 2007, Nat. Protocols, 2, 329; Martinotti, 2020, Epidermal Cells; Methods and Protocols, pp 225-229) was conducted on confluent 4T1 cells incubated with Gal-CPCs (DP=100), Lac-CPCs (DP=100), or Co-CPC-50% at 10, 5, 2.5, or 1 µM with respect to polymer. As controls, an additional set of cells was incubated with either PBS or galactose at 100 µM. After 24 h incubation, cell migration was assessed by measuring the extent to which the scratch closed (Fig.15A). All polymer systems Attorney Docket No.206161-0065-00WO showed a concentration-dependent ability to inhibit 4T1 cell migration (Fig.15B). However, as was observed in the antiproliferation experiments, Gal-CPCs significantly outperformed all other treatment groups and was able to reduce cancer cell migration by 60%, relative to PBS controls (Fig.15C) at the highest concentration tested. In addition, Gal-CPCs were the only system able to significantly suppress cancer cell migration at 5 µM (Fig.15D) and 2.5 µM (Fig. 15E). Example 2: Effect of Polymer Backbone Stereochemistry on CPC Hierarchical Assembly and Biological Function It was found at robust, low dispersity ROMP polymers can be made from all three sugars (mannose, galactose, and glucose) using both exo- and endo-norbornene (Fig.16, Fig.17). Polymerization kinetic studies showed exo monomers rapidly and completely polymerize, while endo monomers convert slowly and only the -OH derivative reaches full conversion (Fig.18, Fig.19). Glucose (Glc) and galactose (Gal) polymerize at approximately the same rate, and mannose polymerizes significantly faster than Glc and Gal (Fig.20, Fig.21, Fig.22). Endo-norbornene polymers behave vastly differently from exo-norbornene polymers which is unintuitive. Exo polymers bind proteins more tightly and more efficiently than endo polymers, whereas endo polymers enter cells much more efficiently than exo polymers, and exo polymers are able to capture Nile Red more efficiently, indicating they have more exposed hydrophobic pockets. It was found that there was also a dependence on sugar, which is unintuitive, wherein galactose and glucose-based polymers showed secondary structures by circular dichroism (CD), but mannose-based polymers do not (Fig.23). CD spectra also showed evidence of secondary structures that were temperature dependent (Fig.24, Fig.25). Galactose and glucose-based polymers form higher order assemblies following dialysis (Fig.26). When dissolved in water, polymers remain unimeric in solution, but when dialysed from DMSO into water, polymers form higher order assemblies (“nanoassemblies”) with slightly altered CD structures. Mannose polymers do not form higher order assemblies, even with dialysis (Fig.27). Endo-Gal and Endo-Glc demonstrate similar behavior (Fig.28), in contrast with Endo-Man (Fig.29). Exo-PNP-Gal nanoassemblies (NAs) also showed temperature-responsive behavior. Attorney Docket No.206161-0065-00WO As the temperature increased, the size of the assembly first increases, then decreases (Fig.30) Exo-PNP-Glc NAs also showed temperature-responsive behavior (Fig.31). The nanoassemblies were imaged using transmission electron microscopy (TEM) (Fig.32). Both Exo-Gal and Exo-Glc polymers showed hydrogen bonding interactions under IR (Fig.33). Dynamic light scattering (DLS) data was used to determine size of the polymers as a function of solvent (Fig.34). Exo polymers were found to more efficiently capture Nile red (hydrophobic dyes) and form micelles. Endo polymers captured significantly less dye, with less micelle formation (Fig.35). The Endo and Exo polymers plus Nile red and corresponding DLSs showed that exo polymers formed micelles with hydrophobic dyes (Fig.36). Exo-Gal polymers also rapidly bind PNA, whereas Endo-Gal polymers show no evidence of protein binding (Fig. 37) and Exo-Gal polymers rapidly bind RCA120, whereas Endo-Gal polymers bind RCA120 much slower (Fig.38). Both exo- and endo-Glc bind ConA, but Endo-glc forms smaller aggregates with ConA at first, before forming larger aggregates like the exo (Fig.39). Both mannose polymers rapidly bind ConA, with endo polymers first forming smaller aggregates, and then larger (Fig.40). Polymer-lectin binding was also measured by microscale thermophoresis (Fig.41) and the cell uptake of polymers as measured by flow cytometry showed that all polymers entered cells, but all endo polymers entered cells to a higher extent than their exo counterparts (Fig.42). In general, the present invention works to leverage the power of carbohydrates and synthetic polymer chemistry to understand and manipulate biology with soft materials (Fig. 43). Galactin-3 was selected as a target as it is upregulated in cancer and other inflammatory diseases (Fig.44) and plays a role in anti-cancer immunity (Fig.45). The ultimate goal of the present invention is to develop CPCs that bind Gal-3 with high avidity and specificity with the hypothesis that the macromolecular structure and presentation of carbohydrates dictates the avidity of galectin-3 binding (Fig.46). Representative monomers (Fig.47) are subjected to ROMP (Fig.48, Fig.49, Fig.50, Fig.51). In these representative studies, Galactose-CPCs were found to bind Gal-3 with micromolar affinity (Fig.52). Derivatives of monomers were further synthesized (Fig.53) and analysis of the resultant polymer showed differences in behavior between Endo-CPCs and Exo-CPCs (Fig.54). Example 3: Synthesis of Glycomonomers and Experimental Procedures Attorney Docket No.206161-0065-00WO All materials and reagents, unless otherwise noted, were purchased from either Sigma Aldrich or Fisher Chemicals. cis-5-Norbornene-exo-2,3-dicarboxylic anhydride was purchased from Oakwood Chemical. (+)-camphor-10-sulfonic acid (CSA) was purchased from TCI chemicals. Benzoyl chloride (BzCl) was purchased from Beantown Chemical. N- iodosuccinimide (NIS), 1,4-dithio-DL-threitol (DTT) were purchased from VWR. Ethyl 1-thio- β-D-glucopyranoside and 4-aminobutan-1-ol were purchased from Ambeed. Dry solvents, dimethylformamide (DMF), dichloromethane (DCM), and methanol (MeOH) were prepared by drying via VAC solvent purification system (SPS), distillation, and sieves respectively. Nuclear magnetic resonance spectra were recorded at ambient temperature unless stated otherwise with an Agilent MR 400 (400 MHz), Varian MR-400 (400 MHz), Bruker NEO400 (400 MHz), Bruker AVIII 3M 500 (500 MHz), or Bruker Avance III HD fitted with a Prodigy cryoprobe (500 MHz). Solvent resonances were referenced for1H and13C NMR chemical shifts and reported in ppm. Multiplicity data reported as s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, and m = multiplet. High resolution ESI-MS was obtained using an Agilent Technologies 6530 Accurate-Mass Q-TOF. Polymer characterization was completed using a Tosoh Bioscience EcoSEC Elite HLC-8420GPC fitted with a TSKgel Alpha-M (0018344) column and a Wyatt DAWN 8 (WD3-03) light scattering detector. The GPC-LS system was run in 10 mM LiBr in DMF at 60 °C. Dynamic light scattering (DLS) measurements were taken using a Zetasizer Nano ZS (Dispersant: H2O RI = 1.330, Viscosity = 0.8872 or 1X PBS RI = 1.332, Viscosity = 0.9043; Material: RI = 1.45, Absorption = 0.001; T = 25 °C) with three runs per measurement, 10 seconds per run, and at least 3 measurements averaged together. All cell lines were obtained from ATCC or Sigma Aldrich. Cells were incubated at 37 °C at 5% CO2using RPMI-1640 (Fisher Scientific, Cat: 11875093) supplemented with 10% fetal bovine serum (Fisher Scientific, Cat: 35010CV), and 1% penicillin / streptomycin (Fisher Scientific, Cat: SV30010). Cells cultures were maintained by subculturing in flasks every 2-5 days as necessary per cell growth using trypsin-EDTA, 0.05% (Fisher Scientific, Cat: MT25052Cl). General synthetic pathways are shown in Fig.55. 6-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl)hexanoic acid: Nor-Hex (1) Attorney Docket No.206161-0065-00WO O H O Carboxylic acid established method (Patel et al., 2012, Biomacromolecules, . 1H NMR (400 MHz, CDCl3) δ: 6.27 (s, 2H), 3.45 (t, J = 7.4 Hz, 2H), 3.26 (s, 2H), 2.66 (s, 2H), 2.33 (t, J = 7.4 Hz, 2H), 1.73 – 1.52 (m, 4H), 1.50 (d, J = 9.9 Hz, 1H), 1.34 (p, J = 8.0 Hz, 2H), 1.20 (d, J = 9.8 Hz, 1H). 3-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl)propanoic acid: Nor-Ala (2) O H Carboxylic acid Xa established method (Zhang et al., 2013, J. Am. Chem. Soc., 135, 15994). 1H NMR (500 MHz, CDCl3) δ: 6.29 (s, 2H), 3.79 (t, J = 7.3 Hz, 2H), 3.28 (s, 2H), 2.74 – 2.61 (m, 4H), 1.52 (d, J = 9.9 Hz, 1H), 1.25 (d, J = 9.9 Hz, 1H). 3-((tert-butyldimethylsilyl)oxy)propan-1-amine (3) TBSONH2TBS protected alcohol Xa was prepared using a previously established method and used without further purification. 1H NMR (500 MHz, CDCl3) δ: 3.64 (t, J = 6.0 Hz, 2H), 2.74 (t, J = 6.8 Hz, 2H), 1.72 (s, 2H), 1.60 (p, J = 6.4 Hz, 2H), 0.83 (s, 9H), -0.01 (s, 6H). N-(3-((tert-butyldimethylsilyl)oxy)propyl)-6-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H- 4,7-methanoisoindol-2-yl)hexanamide: Nor-Hex-Pr-TBS (4) Attorney Docket No.206161-0065-00WO O H O oxy)propan-1- amine (5.4 mmol, 1.5 , were in dry DCM (10 mL). Upon cooling to 0 °C, DCC (7.2 mmol, 2 eq.) dissolved in dry DCM (5 mL) was dripped into the reaction mixture. The ice bath was allowed to expire, and the reaction was stirred at room temperature overnight. The reaction was filtered to remove the precipitated dicyclohexyl urea (DCU) and the filter cake washed with DCM. The reaction mixture was subjected to an aqueous workup consisting of a wash with water followed by drying over Na2SO4and concentration under vacuum. Flash column chromatography was conducted (SiO2: 5% to 50% EtOAc in hexanes) and the title compound 4 was isolated as a yellow oil in 71% yield (1153.17 mg, 2.57 mmol). 1H NMR (500 MHz, CDCl3) δ: 6.28 (s, 2H), 6.15 (s, 1H), 3.73 (t, J = 5.6 Hz, 2H), 3.44 (t, J = 7.5 Hz, 2H), 3.36 (q, J = 5.9 Hz, 2H), 3.26 (s, 2H), 2.66 (s, 2H), 2.11 (t, J = 7.6 Hz, 2H), 1.70 (p, J = 5.9 Hz, 2H), 1.64 (p, J = 7.7 Hz, 2H), 1.56 (q, J = 7.6 Hz, 2H), 1.50 (d, J = 9.9 Hz, 1H), 1.31 (p, J = 8.0 Hz, 2H), 1.20 (d, J = 9.8 Hz, 1H), 0.90 (s, 9H), 0.06 (s, 6H). 13C NMR (126 MHz, CDCl3) δ: 178.20, 172.56, 137.95, 62.84, 47.92, 45.27, 42.86, 38.61, 38.58, 36.74, 31.57, 27.64, 26.77, 26.05, 25.41, 18.35, -5.30. HRMS for C24H40N2O4Si: [M + Na]+calc. = 471.2650; found = 471.2658. N-(3-((tert-butyldimethylsilyl)oxy)propyl)-3-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H- 4,7-methanoisoindol-2-yl)propanamide: Nor-Ala-Pr-TBS (5) O H Carboxylic oxy)propan-1- amine (5.4 mmol, 1.5 eq.), and DMAP (1.44 mmol, 0.4 eq.) were dissolved in dry DCM (10 mL). Upon cooling to 0 °C, DCC (7.2 mmol, 2 eq.) dissolved in dry DCM (5 mL) was dripped into the reaction mixture. The ice bath was allowed to expire, and the reaction was stirred at Attorney Docket No.206161-0065-00WO room temperature overnight. The reaction was filtered to remove the precipitated dicyclohexyl urea (DCU) and the filter cake washed with DCM. The reaction mixture was subjected to an aqueous workup consisting of a wash with water followed by drying over Na2SO4and concentration under vacuum. Flash column chromatography was conducted (SiO2: 5% to 50% EtOAc in hexanes) and the title compound 5 was isolated as a yellow oil in 77% yield (1122.39 mg, 2.76 mmol). 1H NMR (500 MHz, CDCl3) δ: 6.28 (s, 2H), 6.25 (s, 1H), 3.78 (t, J = 7.3 Hz, 2H), 3.72 (t, J = 5.6 Hz, 2H), 3.34 (q, J = 6.0 Hz, 2H), 3.27 (s, 2H), 2.68 (s, 2H), 2.46 (t, J = 7.3 Hz, 2H), 1.69 (p, J = 5.9 Hz, 2H), 1.50 (d, J = 9.9 Hz, 1H), 1.24 (d, J = 9.6 Hz, 1H), 0.89 (s, 9H), 0.06 (s, 6H). 13C NMR (126 MHz, CDCl3) δ: 177.97, 169.32, 137.98, 62.60, 47.95, 45.34, 42.87, 38.55, 35.17, 33.98, 31.49, 26.05, 18.34, -5.30. HRMS for C21H34N2O4Si: [M + Na]+calc. = 429.2180; found = 429.2191. 6-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl)-N-(3- hydroxypropyl)hexanamide: Nor-Hex-Pr-OH (6) in a minimal amount of anhydrous methanol. Acetyl chloride (0.39 mmol, 0.15 eq.) was added to reaction and stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. Flash column chromatography was conducted (SiO2: 80% to 100% EtOAc in hexanes) and the title compound 6 was isolated as a yellow oil in 91% yield (777.95 mg, 2.33 mmol). 1H NMR (400 MHz, MeOD) δ 6.32 (s, 2H), 3.58 (t, J = 6.3 Hz, 2H), 3.45 (t, J = 7.2 Hz, 2H), 3.25 (t, J = 7.0 Hz, 2H), 3.18 (t, J = 1.9 Hz, 2H), 2.71 (s, 2H), 2.17 (t, J = 7.4 Hz, 2H), 1.76 – 1.45 (m, 7H), 1.37 – 1.18 (m, 3H). 13C NMR (101 MHz, MeOD) δ 180.09, 176.09, 138.90, 60.41, 46.31, 43.49, 39.35, 37.34, 36.80, 33.25, 28.46, 27.55, 26.48. HRMS for C18H26N2O4: [M + Na]+calc. = 357.1785; found = 357.1787. Attorney Docket No.206161-0065-00WO 3-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl)-N-(3- hydroxypropyl)propanamide: mono-OH (7) H dissolved in a minimal amount was added to reaction and stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. Flash column chromatography was conducted (SiO2: 80% to 100% EtOAc in hexanes) and the title compound 7 was isolated as a white solid in 67% yield (539.74 mg, 1.85 mmol). 1H NMR (400 MHz, MeOD) δ: 6.32 (s, 2H), 3.73 (t, J = 7.0 Hz, 2H), 3.57 (t, J = 6.3 Hz, 2H), 3.21 (t, J = 7.0 Hz, 2H), 3.18 (s, 2H), 2.70 (s, 2H), 2.46 (t, J = 7.0 Hz, 2H), 1.68 (p, J = 6.6 Hz, 2H), 1.47 (d, J = 9.8 Hz, 1H), 1.30 (d, J = 9.7 Hz, 1H). 13C NMR (101 MHz, MeOD) δ: 179.65, 138.93, 60.40, 49.03, 46.30, 43.59, 37.43, 36.33, 34.69, 33.09. HRMS for C15H20N2O4: [M + Na]+calc. = 315.1315; found = 315.1321. 6-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl)-N-(3- (((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2- yl)oxy)propyl)hexanamide: mono-Gal10 (8) (0.61 mmol, 1.2 eq.) were combined and placed under high-vac overnight. Under N2, a minimal volume of dry DCM was added to the reaction vessel. Following dissolution, the reaction was cooled to 0 °C and BF3 • Et2O (1.53 mmol, 3 eq.) was dripped into the reaction. The reaction was stirred at room temperature for 4 hours followed by another addition of BF3• Et2O (1.53 mmol, 3 eq.). The reaction was stirred overnight and then quenched via the addition of saturated NaHCO3. After the reaction was stirred with saturated NaHCO3 for ten minutes, the mixture was transferred to a separatory funnel. The mixture was separated, and the aqueous layer extracted with DCM (x3). Attorney Docket No.206161-0065-00WO The organic fractions were combined together and washed with dilute brine, dried over Na2SO4, and then concentrated under reduced pressure. Flash column chromatography was conducted (SiO2: 80% to 100% EtOAc in hexanes) to isolate the per-acetylated and per-acetylated minus 1 acetyl- norbornene-galactose conjugates in an 82% crude yield. The aforementioned galactose conjugates were then subjected to base promoted acetyl deprotection. The compounds were dissolved in a minimal amount of MeOH followed by the addition of NaOMe (0.1 mmol, 0.2 eq.). The reaction was monitored via TLC and sequential additions of NaOMe (0.1 mmol, 0.2 eq.) were added until reaction completion. Upon completion, the reaction was quenched with Dowex-X8 H+resin until the pH reached 6 - 7.5. The mixture was rapidly filtered, resin washed with MeOH, and then concentrated under reduced pressure. The crude product was then subjected to flash column chromatography (SiO2: 100% acetone) and the title compound 8 was isolated as a white solid in 37% yield over two steps (77.7 mg, 0.16 mmol). 1H NMR (400 MHz, MeOD) δ: 6.32 (s, 2H), 4.23 (d, J = 7.2 Hz, 1H), 3.93 (m, 1H), 3.83 (d, J = 3.1 Hz, 1H), 3.80 – 3.68 (m, 2H), 3.62 (m, 1H), 3.55 – 3.42 (m, 6H), 3.18 (s, 2H), 2.72 (s, 2H), 2.21 – 2.14 (m, 3H), 1.79 (p, J = 6.3 Hz, 2H), 1.68 – 1.53 (m, 4H), 1.49 (d, J = 10.1 Hz, 1H), 1.31 (m, 3H), 1.21 (d, J = 9.8 Hz, 1H). 13C NMR (101 MHz, MeOD) δ 180.21, 176.04, 138.89, 104.95, 76.68, 75.00, 72.58, 70.34, 68.35, 62.56, 46.31, 43.48, 39.39, 37.61, 36.84, 30.32, 28.45, 27.53, 26.48. HRMS for C24H36N2O9: [M + H]+calc. = 497.2494; found = 497.2502. N-(3-(((2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-(((2S,3R,4S,5R,6R)-3,4,5- trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2- yl)oxy)propyl)-6-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2- yl)hexanamide: mono-Lac10 (9) HO OHOH H O 1.2 eq.) were combined and placed under high-vac overnight. Under N2, a minimal volume of dry DCM was added to the reaction vessel. Following dissolution, the reaction was cooled to 0 °C and BF3 Attorney Docket No.206161-0065-00WO • Et2O (0.87 mmol, 3 eq.) was dripped into the reaction. The reaction was stirred at room temperature for 4 hours followed by another addition of BF3 • Et2O (0.87 mmol, 3 eq.). The reaction was stirred overnight and then quenched via the addition of saturated NaHCO3. After the reaction was stirred with saturated NaHCO3 for ten minutes, the mixture was transferred to a separatory funnel. The mixture was separated, and the aqueous layer extracted with DCM (x3). The organic fractions were combined together and washed with dilute brine, dried over Na2SO4, and then concentrated under reduced pressure. Flash column chromatography was conducted (SiO2: 80% to 100% EtOAc in hexanes) to isolate the per-acetylated and per-acetylated minus 1 acetyl- norbornene-lactose conjugate with a 62% crude yield. The aforementioned lactose conjugates were then subjected to base promoted acetyl deprotection. The compounds were dissolved in a minimal amount of MeOH followed by the addition of NaOMe (0.058 mmol, 0.2 eq.). The reaction was monitored via TLC and sequential additions of NaOMe (0.058 mmol, 0.2 eq.) were added until reaction completion. Upon completion, the reaction was quenched with Dowex-X8 H+resin until the pH reached 6 - 7.5. The mixture was rapidly filtered, resin washed with MeOH, and then concentrated under reduced pressure. The crude product was then subjected to flash column chromatography (SiO2: 0% to 10% MeOH in acetone) and the title compound 9 was isolated as a white solid in 40% yield over two steps (78.2 mg, 0.12 mmol). 1H NMR (400 MHz, MeOD) δ: 6.33 (s, 2H), 4.36 (d, J = 7.5 Hz, 1H), 4.31 (d, J = 7.8 Hz, 1H), 3.98 – 3.66 (m, 6H), 3.66 – 3.38 (m, 10H), 3.30 – 3.22 (m, 2H), 3.18 (s, 2H), 2.71 (s, 2H), 2.17 (t, J = 7.4 Hz, 2H), 1.79 (p, J = 6.4 Hz, 2H), 1.67 – 1.53 (m, 4H), 1.53 – 1.45 (m, 1H), 1.31 (p, J = 8.2 Hz, 2H), 1.22 (d, J = 9.7 Hz, 1H). 13C NMR (101 MHz, MeOD) δ: 180.14, 176.00, 138.90, 105.10, 104.16, 80.66, 77.09, 76.46, 74.84, 74.77, 72.56, 70.30, 68.44, 62.49, 61.93, 46.31, 43.49, 39.38, 37.62, 36.83, 30.32, 28.46, 27.53, 26.48. HRMS for C30H46N2O14: [M + Na]+calc. = 681.2841; found = 681.2857. 3-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl)-N-(3- (((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2- yl)oxy)propyl)propanamide: mono-Gal7(10) Attorney Docket No.206161-0065-00WO O H HO OHO H Alcohol 7 (0.61 mmol, 1.2 eq.) were combined and volume of dry DCM was added to the reaction vessel. Following dissolution, the reaction was cooled to 0 °C and BF3 • Et2O (1.53 mmol, 3 eq.) was dripped into the reaction. The reaction was stirred at room temperature for 4 hours followed by another addition of BF3• Et2O (1.53 mmol, 3 eq.). The reaction was stirred overnight and then quenched via the addition of saturated NaHCO3. After the reaction was stirred with saturated NaHCO3 for ten minutes, the mixture was transferred to a separatory funnel. The mixture was separated, and the aqueous layer extracted with DCM (x3). The organic fractions were combined together and washed with dilute brine, dried over Na2SO4, and then concentrated under reduced pressure. Flash column chromatography was conducted (SiO2: 80% to 100% EtOAc in hexanes) to isolate the per-acetylated and per-acetylated minus 1 acetyl- norbornene-galactose conjugates in 79% crude yield. The aforementioned galactose conjugates were then subjected to base promoted acetyl deprotection. The compounds were dissolved in a minimal amount of MeOH followed by the addition of NaOMe (0.1 mmol, 0.2 eq.). The reaction was monitored via TLC and sequential additions of NaOMe (0.1 mmol, 0.2 eq.) were added until reaction completion. Upon completion, the reaction was quenched with Dowex-X8 H+resin until the pH reached 6 - 7.5. The mixture was rapidly filtered, resin washed with MeOH, and then concentrated under reduced pressure. The crude product was then subjected to flash column chromatography (SiO2: 100% acetone) and the title compound 10 was isolated as a white solid in 32% yield over two steps (74.6 mg, 0.16 mmol). 1H NMR (400 MHz, MeOD) δ: 6.32 (s, 2H), 4.23 (d, J = 7.2 Hz, 1H), 3.92 (m, 1H), 3.82 (d, J = 3.1 Hz, 1H), 3.74 (m, 4H), 3.61 (m, 1H), 3.55 – 3.47 (m, 3H), 3.25 (m, 2H), 3.18 (s, 2H), 2.71 (s, 2H), 2.46 (t, J = 7.0 Hz, 2H), 1.76 (p, J = 6.3 Hz, 2H), 1.47 (d, J = 9.9 Hz, 1H), 1.30 (d, J = 9.7 Hz, 1H). 13C NMR (101 MHz, MeOD) δ: 179.82, 172.85, 138.93, 104.92, 76.70, 75.00, 72.57, 70.34, 68.35, 62.57, 49.05, 46.31, 43.60, 37.70, 36.41, 34.76, 30.16. HRMS for C21H30N2O9: [M + H]+calc. = 455.2024; found = 455.2031. Attorney Docket No.206161-0065-00WO N-(3-(((2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-(((2S,3R,4S,5R,6R)-3,4,5- trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2- yl)oxy)propyl)-3-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2- yl)propanamide: mono-Lac7 (11) O H HO OHOH H mmol, 1.2 eq.) were combined vac a volume of dry DCM was added to the reaction vessel. Following dissolution, the reaction was cooled to 0 °C and BF3• Et2O (0.87 mmol, 3 eq.) was dripped into the reaction. The reaction was stirred at room temperature for 4 hours followed by another addition of BF3 • Et2O (0.87 mmol, 3 eq.). The reaction was stirred overnight and then quenched via the addition of saturated NaHCO3. After the reaction was stirred with saturated NaHCO3for ten minutes, the mixture was transferred to a separatory funnel. The mixture was separated, and the aqueous layer extracted with DCM (x3). The organic fractions were combined together and washed with dilute brine, dried over Na2SO4, and then concentrated under reduced pressure. Flash column chromatography was conducted (SiO2: 80% to 100% EtOAc in hexanes) to isolate the per-acetylated and per-acetylated minus 1 acetyl- norbornene-lactose conjugates in 58% crude yield. The aforementioned lactose conjugates were then subjected to base promoted acetyl deprotection. The compounds were dissolved in a minimal amount of MeOH followed by the addition of NaOMe (0.058 mmol, 0.2 eq.). The reaction was monitored via TLC and sequential additions of NaOMe (0.058 mmol, 0.2 eq.) were added until reaction completion. Upon completion, the reaction was quenched with Dowex-X8 H+resin until the pH reached 6 - 7.5. The mixture was rapidly filtered, resin washed with MeOH, and then concentrated under reduced pressure. The crude product was then subjected to flash column chromatography (SiO2: 0% to 10% MeOH in acetone) and the title compound 11 was isolated as a white solid in 37% yield over two steps (67.3 mg, 0.11 mmol). Attorney Docket No.206161-0065-00WO 1H NMR (400 MHz, MeOD) δ: 6.32 (s, 2H), 4.36 (d, J = 7.5 Hz, 1H), 4.31 (d, J = 7.8 Hz, 1H), 3.96 – 3.39 (m, 16H), 3.25 (t, J = 8.5 Hz, 3H), 3.18 (s, 2H), 2.71 (s, 2H), 2.46 (t, J = 7.0 Hz, 2H), 1.77 (p, J = 6.3 Hz, 2H), 1.47 (d, J = 9.9 Hz, 1H), 1.30 (d, J = 9.8 Hz, 1H). 13C NMR (101 MHz, MeOD) δ: 179.74, 172.85, 138.94, 105.09, 104.15, 80.64, 77.09, 76.48, 74.84, 74.77, 72.56, 70.31, 68.45, 62.50, 61.93, 46.31, 43.62, 37.70, 36.39, 34.77, 30.19. HRMS for C27H40N2O14: [M + Na]+calc. = 639.2372; found = 639.2377. (4aR,6S,7R,8R,8aS)-6-(ethylthio)-2-phenylhexahydropyrano[3,2-d][1,3]dioxine-7,8-diol: (12) Benzaldehyde 2 eq.) and ethyl 1-thio-β-D- glucopyranoside (5.0 mmol, 1 eq.) were dissolved in dry ACN (10 mL). CSA (0.5 mmol, 0.1 eq.) was added into the reaction mixture. The reaction was stirred at room temperature overnight. The reaction was quenched using TEA and subjected to an aqueous workup consisting of a wash with water followed by drying over Na2SO4and concentration under vacuum. Flash column chromatography was conducted (SiO2: 5% to 50% EtOAc in hexanes) and the title compound 12 was isolated as a white foam in 88% yield (1375.92 mg, 4.41 mmol). 1H NMR (500 MHz, CDCl3) δ: 7.52 – 7.45 (m, 2H), 7.41 – 7.33 (m, 3H), 5.55 (s, 1H), 4.47 (d, J = 9.8 Hz, 1H), 4.36 (dd, J = 10.5, 4.9 Hz, 1H), 3.84 (m, 1H), 3.77 (t, J = 10.2 Hz, 1H), 3.58 (t, J = 9.3 Hz, 1H), 3.55 – 3.47 (m, 2H), 2.81 – 2.73 (m, 3H), 2.60 (d, J = 2.1 Hz, 1H), 1.33 (t, J = 7.5 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ: 136.88, 129.32, 128.36, 126.27, 101.95, 86.66, 80.37, 74.58, 73.21, 70.58, 68.60, 24.80, 15.31. HRMS for C15H20O5S: [M + Na]+calc. = 335.9024; found = 335.9032. (4aR,6S,7R,8S,8aR)-6-(ethylthio)-2-phenylhexahydropyrano[3,2-d][1,3]dioxine-7,8-diyl dibenzoate: (13) Attorney Docket No.206161-0065-00WO Benzoyl chloride (16.0 mmol, 4 eq.) and compound 12 (4.0 mmol, 1 eq.) were dissolved in dry pyridine (10 mL). The reaction was stirred at room temperature overnight. The reaction mixture was concentrated under vacuum followed by extraction with DCM / water. The organic layer was dried over Na2SO4 and concentrated under vacuum. Flash column chromatography was conducted (SiO2: 5% to 25% EtOAc in hexanes) and the title compound 13 was isolated as a white foam in 91% yield (1892.80 mg, 3.64 mmol). 1H NMR (500 MHz, CDCl3) δ: 7.95-7.28 (m, 15H), 5.81 (t, J = 9.4 Hz, 1H), 5.55 (s, 1H), 5.51 (t, J = 9.6 Hz, 1H), 4.82 (d, J = 9.9 Hz, 1H), 4.45 (dd, J = 10.5, 4.8 Hz, 1H), 3.93 (t, J = 9.5 Hz, 1H), 3.87 (t, J = 10.3 Hz, 1H), 3.75 (td, J = 9.6, 4.8 Hz, 1H), 2.77 (m, 2H), 1.26 (t, J = 7.5 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ: 165.59, 165.32, 136.74, 133.30, 133.11, 129.88, 129.79, 129.39, 129.18, 129.05, 128.38, 128.30, 128.20, 126.12, 101.48, 84.51, 78.81, 73.21, 71.03, 71.00, 68.59, 24.43, 14.84. HRMS for C15H20O5S: [M + Na]+calc. = 543.1448; found = 543.1446. (3aR,7aS)-2-(4-hydroxybutyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione: (14) 4-aminobutan-1-ol (33.5 and cis-5-norbornene-exo-2,3- dicarboxylic anhydride (30.5 mmol, 1 eq.) were dissolved in dry toluene (20 mL). After adding TEA (1.5 mmol, 0.05 eq.), the reaction was stirred at 110̊ C overnight. The reaction mixture was concentrated under vacuum. Flash column chromatography was conducted (SiO2: 50% to 100% EtOAc in hexanes) and the title compound 14 was isolated as a white foam in 87% yield (6227.73 mg, 26.5 mmol). Attorney Docket No.206161-0065-00WO 1H-NMR (500 MHz, CDCl3): δ = 6.28 (s, 2H), 3.65 (q, J = 5.9 Hz, 2H), 3.54 – 3.45 (m, 2H), 3.26 (s, 2H), 2.67 (d, J = 4.0 Hz, 2H), 2.05 (d, J = 4.7 Hz, 1H), 1.68 – 1.60 (m, 2H), 1.60 – 1.53 (m, 2H), 1.51 (dd, J = 10.1, 7.4 Hz, 1H), 1.21 (d, J = 9.3 Hz, 1H). 13C-NMR (126 MHz, CDCl3): δ = 178.19, 137.81, 62.08, 47.80, 45.14, 42.73, 38.39, 29.81, 24.31. HRMS for C13H17NO3: [M + Na]+calc. = 258.1101; found = 258.1111. (4aR,6R,7R,8S,8aR)-6-(4-((3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7- methanoisoindol-2-yl)butoxy)-2-phenylhexahydropyrano[3,2-d][1,3]dioxine-7,8-diyl dibenzoate: (15) (13) (3.3 mmol, eq.) were dissolved in dry DCM (10 mL) with 3 Å molecular sieves. After adding NIS (5.0 mmol, 1.5 eq.) followed by TMSOTf (0.2 mmol, 0.05 eq.), the reaction was stirred at -40 ̊C for 2 hours. The reaction mixture was quenched by adding TEA and was concentrated under vacuum. The crude product was extracted with water / DCM followed by washing with water. Flash column chromatography was conducted (SiO2: 10% to 60% EtOAc in hexanes) and the title compound 15 was isolated as a white foam in 67% yield (1532.22 mg, 2.21 mmol). 1H-NMR (500 MHz, CDCl3): δ = 8.02 – 7.92 (m, 4H), 7.56 – 7.39 (m, 5H), 7.39 – 7.26 (m, 6H), 6.26 (t, J = 1.9 Hz, 2H), 5.80 (t, J = 9.5 Hz, 1H), 5.57 (s, 1H), 5.48 (dd, J = 9.4, 7.8 Hz, 1H), 4.82 (d, J = 7.8 Hz, 1H), 4.45 (dd, J = 10.6, 4.9 Hz, 1H), 4.02 – 3.84 (m, 3H), 3.72 (td, J = 9.7, 4.9 Hz, 1H), 3.58 (dt, J = 9.4, 5.8 Hz, 1H), 3.43 – 3.30 (m, 2H), 3.25 – 3.16 (m, 2H), 2.60 (s, 2H), 1.54 (m, 4H), 1.48 – 1.40 (d, J = 9.6 Hz, 1H), 1.18 – 1.11 (d, J = 9.6 Hz, 1H). 13C-NMR (126 MHz, CDCl3): δ = 177.91, 165.62, 165.14, 137.79, 136.85, 133.17, 133.10, 129.81, 129.78, 129.44, 129.35, 129.02, 128.38, 128.31, 128.20, 126.14, Attorney Docket No.206161-0065-00WO 101.65, 101.45, 78.85, 72.50, 72.15, 69.49, 68.67, 66.60, 47.74, 45.12, 42.71, 38.04, 26.85, 24.28. HRMS for C40H39NO10: [M + Na]+calc. = 716.2466; found = 716.2465. (3aR,7aS)-2-(4-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2- yl)oxy)butyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione: (16) 15 (0.4 mmol, 1 eq.) were dissolved in dry DCM (10 mL). After adding CSA (0.04 mmol, 0.1 eq.), the reaction was stirred at room temperature for 7 hours. The reaction mixture was quenched by adding TEA and was extracted with ethyl acetate / water. After drying the solvent under vacuum, the crude product was dissolved in dry MeOH (10 mL). After adding NaOME (0.04 mmol, 0.1 eq.), the reaction was stirred at room temperature for 2 hours. The reaction was neutralized with proton exchange resin. Flash column chromatography was conducted (SiO2: 0% to 10% MeOH in DCM) and the title compound 16 was isolated as a white solid in 62% yield (98.46 mg, 0.25 mmol). 1H-NMR (500 MHz, MeOD): δ = 6.35 (t, J = 1.9 Hz, 2H), 4.26 (d, J = 7.8 Hz, 1H), 3.98 – 3.85 (m, 2H), 3.69 (dd, J = 11.9, 5.0 Hz, 1H), 3.59 (d, J = 9.8 Hz, 1H), 3.52 (t, J = 6.9 Hz, 2H), 3.39 – 3.25 (m, 5H), 3.23 – 3.15 (m, 3H), 2.74 (d, J = 1.4 Hz, 2H), 1.73 – 1.58 (m, 4H), 1.55 – 1.48 (m, 1H), 1.26 (d, J = 9.7 Hz, 1H). 13C-NMR (126 MHz, MeOD): δ = 178.79, 137.51, 102.95, 76.68, 76.52, 73.71, 70.25, 68.60, 61.39, 44.91, 42.12, 37.93, 26.74, 24.12. HRMS for C19H27NO8: [M + Na]+calc. = 420.1629; found = 420.1638. General polymerization methods Each polymer was made using these standard conditions unless otherwise stated. Monomer was placed under high vacuum overnight followed by procurement of freshly dried Attorney Docket No.206161-0065-00WO DMF via a VAC solvent purification system (SPS) in an oven dried, N2 backfilled collection flask. The following steps were completed under a nitrogen atmosphere in a PLAS-LABS 810- series glove box. The monomer (or both monomers for Co-CPC generation) was dissolved in DMF followed by addition of the Grubbs M300® catalyst (Sigma: 682330) solution (in DMF) at the target monomer to catalyst ratio to a final catalyst concentration of 1.5 mM. The polymerization was removed from the glove box and sealed using PTFE tape and parafilm. The reaction was heated at 60 °C while shaking at ~1200 rpm using a Benchmark Scientific Heating and Cooling Shaker (H5000-HC) for 2 to 4 hours depending on the target polymer length. Polymer termination was accomplished via the addition of ethyl vinyl ether. Kinetics Kinetics measurements were run on at 60 °C in DMF-d7. The general polymerization method was followed using a J-young air-free NMR tube with a time = 0 point taken prior to catalyst addition and the first time point taken as quickly as the sample could be submitted. The NMR took a1H NMR spectrum every 120 or 180 seconds at least 13 times. Final catalyst concentration was 1.65 mmol for the APOH monomer and 0.6 mM and 0.47 mM for the galactose and lactose glycomonomers, respectively, due to the large quantity of monomer necessary to reach at least 1.5 mM of catalyst in the required minimum NMR volume. Experiments with full length C-terminus his-tag labeled galectin-3 The C-terminus his-tag labeled galectin-3 was first diluted to 800 nm and NTA- Atto-488 fluorophore (Sigma Aldrich: 39625) diluted to 80 nm, both in 1x PBS. A 1:1 solution of galectin-3 and fluorophore was made and set aside while the polymers were diluted. Each polymer was dissolved in 1x PBS to 1 mM followed by a 1:1 serial dilution 16 times with 1x PBS. The highest concentration of the polymer was 200 μM or 500 μM depending on the polymer’s anticipated strength of binding. The galectin-3: fluorophore mixture was added to each polymer solution to create a 1:1 mixture of polymer to fluorescently labeled protein with final fluorophore concentration at 20 nM. The mixture was allowed to incubate at room temperature for 1.5 - 2 hours shieled from light. Once equilibrated, the manufacturer’s instructions were followed to load and run the thermophoresis experiment. The capillary was run at least three times. Attorney Docket No.206161-0065-00WO The data was fit using the Nanotemper Kd model with data originating from 5 or 10 seconds post-laser ignition. The resulting Kd values were then averaged with standard deviation determined. The copolymers made for the MST experiments utilized mono-Gal10 as the galactose monomer and mono-OH7 as the diluent. The copolymers used in the remainder of the manuscript experiments utilized mono-Gal7as the galactose monomer and mono-OH7as the diluent. Coarse-grained mapping of CPCs The three CPC structures, modeled as part of this study, are shown in Fig.56. All structures contained some similarities including - a modified norbornene backbone, consistent side chain groups, and unique functional groups. The backbone and side chain groups of the CPCs were modeled using previously published TOL4, C2M, CCO2, and CON2 beads (An et al., 2019, J. Phys. Chem. B, 123, 909). For the carbohydrate functional groups, however, a novel model with a 2:1 mapping scheme was utilized, to accurately capture the intricate pyranose ring structures of these molecules. The CPC structures were generated using an in-house Python code and their equilibrium bond and angle values were ascertained by mapping CG beads onto energy-minimized atomistic configurations of the side chains obtained from AVOGADRO8. The angles between adjacent side chains of the CPCs were defined to reasonably capture Cis and Trans configurations between side chains. An angle of zero between adjacent side chains was defined as the Cis configuration whereas an angle of 180 degrees was defined as the Trans configuration. All systems were randomly generated with a Cis / Trans ratio of ~50% as shown in Fig.57. The CPCs were solvated in a cubic box of side length 180 Å, with explicit 1-site water beads, each representing 2 water molecules, using the PACKMOL package. CHARMM-type FF equation was used to define bonded and nonbonded interactions between CG beads. Carbohydrate CG model The transferable CG models for amino acids and hydrocarbons developed in previous studies were used to represent the side chains and backbone of CPCs, respectively. β- galactose and β-glucose were mapped according to Fig.56 and tuned to show good agreement with structural (Fig.58, Fig.59) and bulk properties obtained from atomistic (AA) MD Attorney Docket No.206161-0065-00WO simulations using carbohydrate FFs, CHARMM (Guvench et al., 2008, J. Comp. Chem., 29, 2543; Vanommeslaeghe et al., 2010, J. Comp. Chem., 31, 671), GLYCAM06j (Kirschner et al., 2008, J. Comp. Chem., 29, 622), and OPLS-AA (Kony et al., 2002, J. Comp. Chem., 23, 1416). In order to determine whether the modeled CPC systems maintained their structural features throughout the simulations, the dihedral angle autocorrelation function was calculated for all systems (Fig.60) and the lactose CPC showed lowest decay among the three systems (Hanwell et al., 2012, J. Cheminfor., 4, 17; Martinez et al., 2009, J. Comp. Chem., 30, 2157). Furthermore, all systems showed a high autocorrelation (>0.8) indicating that the backbone orientation and tacticity was maintained throughout the simulations. To examine the extent of collapse in different CPCs, the Radius of Gyration (Rg) was calculated for all the systems. Fig.7 shows the evolution of Rg and equilibrated Rg data, respectively, for all three CPCs, averaged over three different starting configurations. It was observed that the extent of the collapse was slightly lower for the lactose homopolymer (Lac- CPC) compared to copolymer (Co-CPC-50%) and galactose homopolymer (Gal-CPC). This can be attributed to the steric effects of the larger disaccharide functional groups attached to the Lac- CPC system. Furthermore, it was found that while the Rgdistribution for the entire CPCs in the Co-CPC, and Gal-CPC systems was similar, the backbone Rgfor the galactose homopolymer system was lower compared to the other systems pointing towards a more collapsed backbone. General procedure for dynamic light scattering (DLS) Each polymer was dissolved in 18.2 MΩ water (milliQ water) or 1X PBS and placed on a rocker for at least 8 hours. The sample was then transferred to a disposable plastic cuvette and was analyzed using a Zetasizer Nano ZS (Dispersant: H2O RI = 1.330, Viscosity = 0.8872 or 1X PBS RI = 1.332, Viscosity = 0.9043; Material: RI = 1.45, Absorption = 0.001; T = 25 °C) with three runs per measurement, 10 seconds per run, and at least 3 measurements averaged together. Galectin-3 Western Blot Cells (4T1 or LNCaP) were washed with PBS and lysed using RIPA buffer with Halt phosphatase and protease inhibitor cocktail (Thermo Fisher: 78440). Protein concentration of the cell lysate was determined using the Pierce BCA assay (Thermo Fisher: 23225, 30 Attorney Docket No.206161-0065-00WO minute, 37 °C protocol).15 μg of protein was incubated at 60 °C for 15 minutes with Laemmli loading dye and 100 mM DTT. Samples were separated in 4-20% SDS-PAGE gel and transferred to a low fluorescence PVDF membrane. The membrane was blocked with Licor Intercept blocking buffer then washed with PBST. The membrane was incubated with a 1:500 dilution of anti-galectin-3 (Thermo Fisher: 14-5301-82) and 1:2000 dilution of anti-beta tubulin (Thermo Fisher: MA516308) in Licor Intercept blocking buffer at 4 °C overnight. Following incubation, the membrane was washed with PBST then was incubated with 1:1000 dilution of goat anti-rat 647 (Thermo Fisher: A21247) and 1:1,000 of goat-anti mouse 488 (Thermo Fisher: A28175) in Licor Intercept blocking buffer for 120 minutes at room temperature in the dark. The membrane was washed with PBST followed by PBS then imaged with a ChemiDoc Imaging Station. Cytotoxicity Cells were seeded in a 96-well plate at 2,500 cells per well for both 4T1 and LNCaP lines. Following growth overnight, cells were treated with PBS, galactose (1 mM), glucose control polymer (10 μM), or experimental treatment polymers at final concentrations of 10 µM. At 4 hours post treatment, CCK-8 assay (Fisher Scientific: NC9864731) was performed per the manufacturer’s instructions. The plate was analyzed using a BioTek Synergy H1 microplate reader. Cellular viability / proliferation Cells were seeded in a 96-well plate at 2,500 cells per well for both 4T1 and LNCaP lines. Following growth overnight, cells were treated with PBS, galactose (1 mM), glucose control polymer (10 μM), or experimental treatment polymers at final concentrations of 10 µM. At 24 hours post treatment, CCK-8 assay (Fisher Scientific: NC9864731) was performed per the manufacturer’s instructions. The plate was analyzed using a BioTek Synergy H1 microplate reader. Live cell Internalization Cells were seeded in Nunc™ Lab-Tek™ II Chambered Coverglass (Thermo Fisher: 155409) at 50,000 cells per well. Following growth overnight, cells were treated with Attorney Docket No.206161-0065-00WO Cy5 labeled Gal-CPC, DP = 100 polymer at 5 μM for 4 hours. Cells were washed twice with PBS and then stained with CellBrite™ Steady 488 Membrane live cell stain (Biotium: 30106-T) via the media exchange protocol for 30 minutes. Cells were then washed twice with media and imaged using a Nikon W1 spinning disk confocal microscope. Images were taken with a 20X (Plan Apochromat λ 20x; NA - 0.75; WD - 1.0 mm) or 100X (Plan Apochromat λ 100x (Oil); NA - 1.45; WD - 0.13 mm) objective. Fixed cell internalization with galectin-3 antibody staining Cells were seeded in Nunc™ Lab-Tek™ II Chambered Coverglass (Thermo Fisher: 155409) at 50,000 cells per well. Following growth overnight, cells were treated with Cy5 labeled Gal-CPC DP = 100 polymer at 5 μM for 4 hours. Cells were washed 4x with PBS and then incubated in 4% PFA for 20 minutes. Cells were permeabilized 3x with PBS followed by incubation for 10 minutes in a 0.1% w / v saponin solution in PBS. Cells were rinsed 3x with PBS for 5 minutes each. Cells were then blocked (PBS with 0.1% saponin and 10% normal goat serum (NGS)) for 1 hour. The cells were incubated in a 1:100 dilution of anti-galectin-3 (Thermo Fisher: 14-5301-82) in PBS with 1% NGS and 0.1% saponin at 4 °C overnight. The cells were rinsed 4x in PBS for 5 minutes each followed by incubation with a 1:1000 dilution of goat anti-rat Alexa fluor-488 (Thermo Fisher: A11006) in PBS with 1% NGS and 0.1% saponin for 1 hour in the dark. The cells were washed 3x with PBS for 5 minutes each followed by counterstaining with DAPI following the manufacturers recommendations (Thermo Fisher: R37606) for 5 minutes. The cells were then washed 3x with PBS and kept hydrated until imaging. Images were taken using a Nikon W1 spinning disk confocal microscope with a 20X (Plan Apochromat λ 20x; NA - 0.75; WD - 1.0 mm) or 100X (Plan Apochromat λ 100x (Oil); NA - 1.45; WD - 0.13 mm) objective. Scratch assay Cells were seeded in a 24-well plate and allowed to grow until confluent. Following confluence, a p200 micropipette tip was used to make scratches in each well. The media was changed to remove upended cells and the wells were imaged using a Nikon SMZ800N Stereoscope fitted with a Nikon DS-Ri2 color camera. Wells were then treated with PBS, galactose (1 mM) or experimental treatment polymers at final concentrations of 1, 2.5, 5, Attorney Docket No.206161-0065-00WO or 10 µM. Following treatment for 24 hours, cells were imaged then fixed in 4% PFA and stained with crystal violet. Cells were imaged again. Analysis of the scratches was completed using ImageJ. The width of each scratch was determined by drawing 10 individual horizontal lines across the scratch, making sure to measure the width along the entirety of the scratched area. All measurements were then averaged together and compared to the average of 10 individual horizontal lines across each scratch at 24 h. Ultimately, the complex, multifunctional role of carbohydrates in biology relies not solely on their molecular composition, but also on their broader macro- and supramolecular architecture. As such, the emergence of novel methodologies aimed at interrogating and understanding the functions of glycans in biological contexts presents exciting prospects for delving deeper into the intricacies of the natural world. In this vein, CPCs have been developed herein as tools for dissecting the impact of carbohydrate multivalency on β-galactoside recognition by Gal-3, a pivotal player in both health and disease. Present investigations have found that maximum grafting density is required for optimal recognition of the present materials by this lectin, highlighting the dominance of multivalency over individual ligand specificity in fostering high avidity interactions. Furthermore, computational analyses reveal that fully grafted CPCs boast the greatest solvent accessible surface area due to reduced carbohydrate- carbohydrate interactions, offering valuable insights into the spatial organization of glycans in the glycocalyx and their mode of interaction with Gal-3. This knowledge translates into substantial advancements in the biological function of these materials, as evidenced by the ability of Gal-CPCs to effectively suppress both the proliferation and migration of 4T1 triple negative breast cancer cells. Thus, these materials not only advance fundamental comprehension of glycans in biology but also offer a promising route for cancer therapeutics from readily available, simple β-galactosides. Example 4: Glucose-Functionalized Polymers for Penetrating the Blood-Brain Barrier The main method of transport of glucose across the blood-brain barrier (BBB) is via glucose-transporter protein 1 (GLUT1). GLUT1 is expressed extensively, and almost exclusively, on the BBB. To enhance the multivalent effect, previous systems have utilized Attorney Docket No.206161-0065-00WO terminally-tagged glucose moieties which cluster based on micellar supramolecular assembly. Pioneering work in this field has relied on complex, multiblock nanoparticulate formulations to drive self-assembly. The present invention exploits active transport mechanisms of cargo across the BBB for therapeutic delivery and targets the BBB using glucose-tagged materials. While the brain constitutes only 2% of a human body’s mass, the brain consumes 20% of glucose which has allowed the use of glucose as BBB targeting ligand. One target of glucose on the BBB is Glucose transporter 1 (GLUT1), which is expressed extensively on the BBB. Single glucose molecules have low affinity to GLUT1 (Deng et al., 2014, Nature, 510, 121), but affinity is increased when multiple glucose molecules are clustered, demonstrating a multivalent effect. The present invention seeks to maximize multivalent interactions with the GLUT1 transporter protein on the BBB (blood brain barrier) to investigate transport mechanisms and optimize delivery of therapeutic cargo. Polymeric systems with multiple copies of glucose incorporated as a core structural facet have been designed and synthesized utilizing “graft-through” polymerization and multivalency can be mimicked through assembly of polymer chains terminally tagged with glucose. Towards this end, norbornene-functionalized glucose derivatives are polymerized through ring-opening metathesis polymerization (ROMP), a technique known for its high functional group tolerance and allowance for flexible monomer design. In solution, these polymers form stable nanoscale aggregates. Where polymeric glucose comprises the hydrophilic corona for binding to GLUT1 on the BBB. Not only does this approach serve to greatly increase glucose density, but it enables the ability to precisely program individual glucose spacing and distance from the polymer backbone. The present invention readily binds to GLUT1 receptors and forms stable homopolymer aggregates. Additional benefits include high glucose density, involve scalable chemistry, and a simple formulation. Beyond including glucose as an integral structural component of these systems, the position of glucose linkage to the polymer backbone influences its ability to bind to GLUT1. Carbohydrates contain six carbons and five chemically distinct hydroxyl groups. Protein binding is often dependent on a highly specific binding orientation; it may involve all hydroxyl groups present, or only a select few. While the crystal structure of GLUT1 has been recently solved, the precise binding orientation of glucose remains ill-defined. Empirical studies suggest that the Attorney Docket No.206161-0065-00WO position 3 and 4 hydroxyl are critical for binding, while the 1, 2, and 6 position are involved, but are less crucial. To probe this question, the structure-function relationships between glucose derivatization and GLUT1 binding capability were studied, particularly in the context of a large macromolecular species. Using glucose functionalized nanomaterials, transport across the BBB has been proven possible through the targeting of GLUT1 with liposomes and polymeric nanoparticles. The major drawback of this general methodology is that single (“monomeric”) glucose molecules have a relatively low binding affinity to GLUT1. However, the affinity can be greatly increased if there are several glucose molecules presented in close proximity, a phenomenon known as the multivalent effect. The invention of these polymeric aggregates incorporating multiple copies of glucose would maximize this effect. This invention can also control for the number of glucose monomers incorporated on the polymer, which can help to evaluate the effect on binding and transport through GLUT1. The dense presentation of glucose on the outer corona of the nanoparticles will maximize interactions with GLUT1 and improve transport efficacy across the BBB, serving as a flexible template in the design of future carbohydrate-based delivery systems. By exercising a “graft-through” approach, the present polymers contain a significantly higher density of glucose per monomeric unit and do not require use of nanoparticles. This maximizes multivalent potential and decreases probability of liver sequestration due to the smaller size. Given the simpler nature of uniform polymer chains, both conceptually and synthetically, this will serve as a stable development platform for future therapeutic delivery vehicles. However, synthesis of carbohydrate derivatives is inherently complex and laborious. To overcome this, extensive time has been spent developing efficient and scalable synthetic routes that can be readily replicated. Given the ubiquity of glucose receptors in the body, there is also reasonable likelihood of off-target delivery. This lack of selectivity can be overcome in vivo by putting the organism under glycemic control, e.g., a state of starvation. This enhances the physiological priority of brain function over other organs, greatly increasing GLUT1 expression and downregulating expression in other tissues. The pendant glucose residues on the polymer may also be susceptible to enzymatic cleavage, greatly lowering their stability. There are several built-in approaches in this project to overcome this. First, the Attorney Docket No.206161-0065-00WO substantial glucose density per-polymer leads to high ligand redundancy; if enzymatic degradation is sufficiently slow then there will still be many copies of glucose present. Second, three derivatives with functionalization at different positions of glucose likely respond differently to the same enzymes, potentially allowing for an inherent degree of biorthogonality. Other potential uses of the present invention include, but are not limited to, pharmaceuticals, therapeutic delivery to brain, fundamental GLUT1 binding knowledge, and treatment of cancerous tumors. It has previously been shown that glucose-tagged polymers will cross the BBB (Li et al., 2017, Nature Communications, 8, 1001; Odom et al., 2024, Nanoscale, 16, 3969). Thus, a hypothesis of the present example was that incorporating glucose directly on to a polymer backbone will maximize multivalent interactions with GLUT1 and improve BBB transport. The materials of the present invention provide uniquely tailored control over structure, density, spacing, and linkages. A goal is to leverage glucose-GLUT1 binding to increase BBB transport. It was found that C3 and C4 positions on glucose are critical for GLUT1 binding (Fig.61). The current synthetic plan was developed after finding that metathesis polymerization of triazole linked monomers led to low metathesis activity and poor reproducibility. General considerations included that the reactions and purification needed to be scalable, and that the protecting group could not be cleavable by hydrogenation or strong acids particularly in aqueous media where water addition to the alkene could occur. A representative synthetic scheme of 1-linked glucose monomer is shown in Fig. 62. A representative synthetic scheme of 3-linked glucose monomer is shown in Fig.63. A representative synthetic scheme of 6-linked glucose monomer is shown in Fig.64. Polymerization was performed using a Grubbs-type ROMP catalyst and resulted in a controlled low dispersity polymerization achieved with alkyl linked monomers (Fig.65). It was determined that azido-sugars could be synthesized in high yield but were unsuccessful in polymerization, but 1-glucose, 3-glucose, and 6-glucose monomers could successfully be syntheized and polymerized via ROMP with low dispersity. It was hypothesized that nucleophilic addition was inhibited by the bicyclic ring system and an alternative route to 3- Attorney Docket No.206161-0065-00WO azido glucose was designed (Fig.66). A representative synthetic scheme for the hydrophilic and hydrophobic monomers is shown in Fig.67. Next, the involvement of GLUT1-mediated internalization in the uptake of the polymers was investigated. To test this, phloretin, a GLUT1 inhibitor, and flow cytometry (Fig 68) were utilized for analysis of polymer uptake. In the flow cytometry setup, forward scattering and side scattering provide information about the size and granularity of cells. MDA-MB-231 cells, human breast cancer cells known to upregulate GLUT1, were cultured in 6-well plates at a density of 1,000,000 cells per well. After 24 hours, cells were incubated with 50 µM phloretin for 30 minutes. Subsequently, 10 µM of either the 10-mer, 50-mer, or 100-mer 1-glucose polymers were added to wells, with and without phloretin treatment. Following a 1-hour incubation, cells were trypsinized, centrifuged, and washed three times with PBS. Cells were then fixed in 4% paraformaldehyde and resuspended in PBS for subsequent flow cytometry analysis. Flow cytometry was employed to evaluate polymer internalization, with measurements of scattered light for cell morphology and fluorescence emission for polymer uptake. The data revealed an unexpected trend in polymer internalization. Contrary to the initial hypothesis, which predicted the greatest uptake for the 100-mer due to multivalent interactions, the 10-mer exhibited the highest internalization, while the 100-mer showed the lowest. Phloretin treatment resulted in inhibition of polymer uptake (Fig.69). A subsequent experiment with a 4-hour polymer incubation period revealed a dramatic increase in median fluorescence intensity for the 10-mer, which almost doubled compared to the 1-hour incubation, while the uptake of the 50-mer and 100-mer remained unchanged. Phloretin treatment again showed a reduction in polymer uptake, though not to the extent necessary to conclusively determine GLUT1-mediated internalization (Fig.70). It was found that the polymers either utilized a secondary uptake mechanism or outcompete phloretin (Fig.71). To further explore the influence of polymer structure on internalization, 3- glucose functionalized polymers were synthesized and tested under identical conditions (Fig. 72). It was hypothesized that attaching the glucose at the 3-position should lead to a decrease in uptake. Flow cytometry analysis of the 10-mer showed a significant decrease in cellular internalization when the functionalization was shifted from the 1-position to the 3-position. In Attorney Docket No.206161-0065-00WO contrast, the 100mer showed the greatest amount of internalization for the 3-glucose polymers. These findings suggest that the position of attachment to the glucose moiety plays a critical role in receptor binding. The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations.

Claims

Attorney Docket No.206161-0065-00WO CLAIMS What is claimed is:

1. A method comprising the step of administering to a subject a composition comprising a carbohydrate-polymer conjugate comprising a structure represented by Formula (I):wherein: A represents a repeat unit selected from the group consisting of C5-C7 alkyl, C5-C7 heteroalkyl, C5-C7aryl, C5-C7heteroaryl, and C5-C7cycloalkyl; n represents an integer from 2-500; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate; and wherein the carbohydrate-polymer conjugate crosses the blood-brain barrier.

2. The method of claim 1, wherein the composition further comprises a therapeutic agent.

3. The method of claim 2, wherein the therapeutic agent is selected from the group consisting of a small molecule, an anticancer agent, an antibody, an immunomodulatory agent, a chelating agent, an imaging agent, and combinations thereof.Attorney Docket No.206161-0065-00WO 4. The method of claim 2, wherein the composition delivers the therapeutic agent across the blood brain barrier of the subject.

5. The method of claim 1, wherein the composition binds to a glucose transporter.

6. The method of claim 1, wherein the composition binds to GLUT-1.

7. The method of claim 1, wherein A comprises one of the following structures: wherein:the wave line represents a bond to L; X represents O, S, NR1, or CR2R3; R1, R2, and R3each independently represent a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30 alkyl, C1-C30 alkyl halide, C1-C30 alkoxy, and any combination thereof; and each structure is independently optionally further substituted.

8. The method of claim 1, wherein L comprises a C1-C30alkyl which is optionally further substituted.

9. The method of claim 1, wherein L is represented by one of the following structures:Attorney Docket No.206161-0065-00WOthe wavy line represents a bond to A; * represents a bond to the carbohydrate; and R’ represents a substituent selected from the group consisting of hydrogen, halide, hydroxy, C1-C30alkyl, C1-C30alkyl halide, C1-C30alkoxy, and any combination thereof.

10. The method of claim 1, wherein the carbohydrate is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, and any combination thereof.

11. The method of claim 1, wherein the carbohydrate is selected from the group consisting of glucose, mannose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, and any stereochemical isomer thereof.Attorney Docket No.206161-0065-00WO 12. The method of claim 1, wherein the carbohydrate is glucose.

13. The method of claim 1, wherein the carbohydrate-polymer conjugate is a copolymer comprising a repeating unit of at least two monomers, wherein at least one monomer comprises glucose.

14. The method of claim 1, wherein L forms a direct bond to the C1-, C3-, or C6-hydroxyl group of the carbohydrate.

15. The method of claim 1, wherein n is between 2 and 100.

16. The method of claim 1, wherein the carbohydrate-polymer conjugate comprises the following structure: .

17. The method of claim 1, wherein the carbohydrate-polymer conjugate comprises the following structure: .Attorney Docket No.206161-0065-00WO 18. A method for eliciting a therapeutic effect of a therapeutic agent, comprising administering to a subject in need thereof a composition comprising a therapeutic agent and a carbohydrate-polymer conjugate comprising a structure represented by Formula (I):wherein: A represents a repeat unit selected from the group consisting of C5-C7alkyl, C5-C7heteroalkyl, C5-C7 aryl, C5-C7 heteroaryl, and C5-C7 cycloalkyl; n represents an integer from 2-500; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate; and wherein the composition delivers the therapeutic agent across the blood brain barrier.

19. The method of claim 18, wherein the subject has a central nervous system disorder selected from the group consisting of depression, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, stroke, head trauma, spinal cord injury, multiple sclerosis, dementia with Lewy Bodies, retinal degeneration, epilepsy, psychiatric disorders, disorders of hormonal balance, and cochlear degeneration.

20. The method of claim 18, wherein the subject has a tumor of the central nervous system (CNS) selected from the group consisting of astrocytomas, glioblastomas, oligodendrogliomas,Attorney Docket No.206161-0065-00WO ependymomas, meningiomas, schwannomas, pituitary tumors, lymphomas, and secondary CNS tumors.

21. A carbohydrate-polymer conjugate comprising a structure represented by Formula (I):wherein: A represents a repeat unit selected from the group consisting of C5-C7 alkyl, C5-C7 heteroalkyl, C5-C7 aryl, C5-C7 heteroaryl, and C5-C7 cycloalkyl; n represents an integer from 2-9; L represents a divalent organic linker; and wherein L forms a direct bond to the carbohydrate.

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