1511 results about "Covalent modifier" patented technology

The invention discloses a probiotic-polyphenol nanoparticle colon-targeted co-delivery system as well as a preparation method and application thereof, and belongs to the field of biological medicines. The FCPs and hyaluronic acid (HA) are combined through non-covalent interaction, so that the hydrogel has colon targeting property and mucosal adhesion at the same time, and delivery of probiotics is facilitated. The hydrogel (HF) based on polysaccharide has good biocompatibility, and can be used for effectively encapsulating the probiotics and the natural products. Then, the PDA-TH NPs and BA are incorporated into the polysaccharide chain network of HF, and finally the BA-HF-PDAT targeted co-delivery system is constructed. The BA (at) HF-PDAT targeted co-delivery system can protect BA from serious gastrointestinal stress, and is jointly assembled with PDT-TH NPs to realize dual slow release of thymol (Thy), so that the treatment effect of BA and Thy is improved, and the BA (at) HF-PDAT targeted co-delivery system contributes to treatment of clostridium difficile infection (CDI).

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

The invention relates to a ligand-effector moiety provided with at least one saponin and antibody-effector moiety provided with at least one saponin. An aspect of the invention is a composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention. The invention also relates to an antibody-drug conjugate comprising covalently linked saponin and to an antibody-oligonucleotide conjugate comprising covalently linked saponin. An aspect of the invention relates to a pharmaceutical composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin, for use as a medicament. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention for use in the treatment or prophylaxis of a cancer.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The invention discloses a gradient frame membrane and separation application thereof. An integrated gradient membrane material is constructed in a mode of functional group sharing, metal node sharing or skeleton interpenetration, and target molecule recognition sites are designed by utilizing the advantage that a framework material is easy to modify, so that the separation performance is remarkably improved. The gradient film structure comprises a metal organic-metal organic framework gradient film, a metal organic-covalent organic framework gradient film and a covalent organic-metal organic framework gradient film. The invention introduces a new structure of a metal organic framework-covalent organic framework gradient film and a construction strategy thereof in detail. The preparation method comprises the steps of preparing a bottom layer film structure from bottom to top, then preparing a top layer film structure on the bottom layer film structure, performing post-modification and the like. By designing a specific asymmetric porous structure and adsorption sites, the membrane shows excellent ethylene / ethane, propylene / propane, ion screening and organic matter dehydration separation performance under the dual action of adsorption selection and shape-selective screening.

Aspects of the disclosure relate to methods of reducing expression or activity of DUX4 (e.g., DUX4 protein and / or mRNA) and / or methods of treating facioscapulohumeral muscular dystrophy (FSHD) in a subject. In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., an RNAi oligonucleotide such as an siRNA) covalently linked to an antibody (e.g., anti-TfRl antibody).

The invention relates to the field of biological medicine, in particular to a hair follicle targeted delivery system and hair growth and hair loss prevention cosmetics, the hair follicle targeted delivery system comprises: a lipid nanoparticle core which is internally loaded with a bioactive component with hair growth and hair loss prevention effects; the hair follicle targeting molecule can specifically recognize and bind to a receptor on the surface of a hair follicle cell; a targeting anchoring conjugate composed of a linker covalently linked to the hair follicle targeting molecule and an anchoring lipid; wherein the targeting anchoring conjugate is embedded into the lipid bilayer of the lipid nanoparticle core through the anchoring lipid, so that the hair follicle targeting molecule is displayed on the surface of the lipid nanoparticle core. According to the application, through an innovative targeted anchoring conjugate structure, the targeting property and enrichment efficiency of hair growth and hair loss prevention active ingredients on hair follicle tissues can be remarkably improved, and the effect that a medicine accurately acts on a focus part is ensured, so that the number of hair follicles at an alopecia areata modeling part can be remarkably increased.

The invention discloses an enzyme immobilization method based on charge directed crosslinking, and belongs to the technical field of enzyme immobilization. The method sequentially comprises the following steps: reacting an enzyme with a modifier containing an anionic group to generate an electronegative modified enzyme; dissolving a protonated amino carrier in an acidic buffer solution to form a first solution, and dispersing a dissociation anion group-containing carrier and a modification enzyme in an alkaline buffer solution to form a second solution; mixing the two solutions, and constructing a gel network immobilized enzyme through electrostatic crosslinking; and finally, strengthening the gel network by using a multivalent metal ion solution. Directional anchoring of the enzyme in the gel is achieved through charge matching, the network stability and the enzyme microenvironment are synchronously optimized in combination with metal ion coordination, use of a covalent cross-linking agent is avoided in the whole process, conformation damage of an enzyme active center is avoided, the activity retention rate, the operation half-life period and the substrate mass transfer efficiency of the immobilized enzyme are remarkably improved, and the immobilized enzyme has good application prospects. The method is suitable for efficient immobilization of industrial enzymes such as beta-glucosidase, and has high biocompatibility and industrial potential.

Aspects of the disclosure relate to complexes comprising an anti-TfR1 antibody covalently linked (e.g., via a linker such as a peptide linker) to a lysosomal enzyme (e.g., an acid alpha glucosidase enzyme), and methods of making and using the fusion complexes to treat a lysosomal storage disease (e.g., Pompe disease).

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

The invention relates to an acylhydrazone bond-connected covalent organic framework material, in particular to an acylhydrazone bond-connected covalent organic framework material as well as a preparation method and application thereof, and aims to overcome the defects of various materials for adsorbing Pd (II) in one aspect or the defects of poor stability and durability in high-acidity and high-radioactivity environments. Or the adsorption selectivity on Pd (II) is not strong. As an emerging crystalline organic porous polymer, the covalent organic framework is mainly formed by connecting pure organic structural units through dynamic covalent bonds, has the advantages of permanent high porosity, low density, high chemical stability, high thermal stability and the like, and is expected to realize Pd (II) adsorption in strong acid and ray irradiation environments.

The invention discloses starch-collagen composite hydrogel as well as a preparation method and application thereof. Collagen is catalyzed by microbial transglutaminase to form a covalent cross-linked network, and meanwhile, hydroxypropyl starch is introduced to construct a physical interpenetrating network through molecular chain penetration and hydrogen-bond interaction; and chondroitin sulfate is further integrated to strengthen the network structure and biological activity through electrostatic interaction. The method is mild in condition and does not need a toxic chemical cross-linking agent, the obtained composite hydrogel has an interpenetrating double-network structure and has excellent mechanical properties, enzymatic degradation resistance and cell affinity, the compression modulus of the composite hydrogel is remarkably improved, the composite hydrogel can keep structural stability for a long time in a collagenase environment, cell adhesion and proliferation can be effectively promoted, and the composite hydrogel has a good application prospect. The hydrogel can be widely applied to tissue engineering scaffolds, wound dressings, drug sustained-release carriers and cartilage repair materials.

The invention provides a covalent organic framework material as well as a preparation method and application thereof, 1, 3, 6, 8-tetra (4-aminophenyl) pyrene is selected as a central construction unit, and a trap state is realized in a covalent organic framework (COFs) by regulating and controlling the symmetry of active sites (benzothiadiazole, BT). Compared with a centrosymmetric counterpart in the COFs, by breaking the symmetry of the center BT core, the trap state density in the COFs can be remarkably reduced, and the service life of the shallow trap state can be prolonged to 1160.02 picoseconds. Therefore, more photo-induced electrons can participate in the photocatalytic reaction, and the remarkable performance (greater than 99%) of photocatalytic reduction of uranium (VI) is finally realized. According to the invention, the key effect of symmetric breaking in inhibition of excited state decay of COFs is clarified for the first time, and a profound solution is provided for understanding how to improve the photocatalytic performance of COFs in environmental restoration.

The invention discloses an oligonucleotide intracellular nano delivery system based on polypeptide modification and application thereof. The system is composed of a periostin targeting sequence (SDSSD), a matrix metalloproteinase 2 (MMP2) response sequence (GPAGLLG), a cell penetrating sequence (RRRRRRRR, R9), a reactive oxygen species (ROS) scavenging and adhesion enhancing group (Gly-DOPA)) and a terminal dibenzocyclooctyne (DBCO) modified engineered polypeptide SDSSD-PEG5-YGFGG-GPAGLLG-R9-(G-DOPA) 3-K4-C-DBCO, and a target oligonucleotide miRNA-26a-A5-Azido modified by 5-polyadenylic acid (AAAAA) and an azide group (Azido), and the target oligonucleotide miRNA-26a-A5-Azido, the target oligonucleotide and assembling through a click chemical reaction and a non-covalent interaction. The nano system has good bone targeting, enzyme responsiveness, intracellular delivery effect and biological safety, can realize stable and efficient delivery of therapeutic oligonucleotides in vivo, and significantly improves the utilization efficiency and therapeutic potential of oligonucleotides. The oligonucleotide intracellular nano delivery system has a wide application prospect in the fields of clinical transformation and precise treatment of oligonucleotide drugs.

A pharmaceutical composition comprises a GPCR agonist fusion protein in which a GPCR agonist peptide is covalently coupled to albumin via a linker in a manner that is resistant to a retro-Michael addition. Advantageously, compositions presented herein avoid decoupling of the agonist form the albumin while retaining the agonist in a steric relationship to the albumin that allows for effective binding and activation of the GPCR while also enabling gp60-mediated transcytosis and FcRn-mediated albumin recycling. These properties enable ultra-low dosages for the GPCR agonist fusion protein to give a therapeutic effect while substantially reducing or even entirely avoiding adverse effects otherwise commonly associated with unbound agonists. Such retro-Michael resistant composition is generally achieved by conformational modification of the albumin, resulting in stereoselective coupling of the linker to the albumin.

Provided in the present invention are a preparation method for a crown ether covalent organic framework material, and the use thereof in iodine adsorption. In the present invention, an 18-crown-6-ether group is introduced into the structure of a covalent organic framework (COF) material for iodine adsorption work. The covalent organic framework material can form a one-dimensional pore channel structure in order, and the 18-crown-6-ether can be selectively complexed with iodine molecules, thereby achieving the purpose of efficient iodine adsorption. The material can perform specific iodine adsorption from high-temperature iodine steam, and the iodine steam adsorption capacity of the COF material is as high as 5.56 g / g. The COF material has a high adsorption capacity, is easy to prepare and simple to operate, has a high adsorption efficiency, and is particularly suitable for adsorbing and separating radioactive iodine in the nuclear industry.

The invention discloses a covalent organic framework with oxidation-reduction activity and a bionic nano-channel structure as well as a preparation method and application of the covalent organic framework, and belongs to the technical field of environmental protection. According to the preparation method, 2, 4-dihydroxybenzene-1, 3, 5-tricarboxaldehyde and 2, 5-bis (allyloxy) terephthaloyl hydrazine are taken as raw materials, a two-dimensional covalent organic framework with oxidation-reduction activity is synthesized, and then a sulfonic acid group with negative charges is covalently grafted, so that a functional material with a bionic nano-channel structure is formed. The material has regular porous channels and rich functional sites, the porous channels provide efficient mass transfer paths and adsorption spaces for uranyl ions, and the functional sites realize specific recognition of the uranyl ions through oxidation-reduction reaction and electrostatic interaction, so that the material shows synergistic advantages of strong selectivity, high adsorption capacity and rapid adsorption kinetics on uranium. The method is simple and low in cost, and the prepared material is clear in structure, good in hydrophilicity, capable of efficiently adsorbing uranyl ions and good in application prospect.

A pharmaceutical composition comprises a GPCR agonist fusion protein wherein the GPCR agonist peptide is covalently conjugated to an albumin via a linker in a manner that is resistant to a reverse Michael addition. Advantageously, the compositions presented herein avoid uncoupling of the agonist to the albumin while maintaining the agonist and the albumin in a spatial relationship that allows efficient binding and activation of the GPCR while also enabling gp60-mediated endocytosis transport and FcRn-mediated albumin recirculation. These characteristics enable ultra-low doses of GPCR agonist fusion proteins to produce therapeutic effects while significantly reducing or even completely avoiding side effects that would otherwise be typically associated with unbound agonists. Such reverse Michael resistant compositions are typically achieved by conformationally modifying an albumin, resulting in a stereoselective coupling of a linker to the albumin.

The invention discloses a full-conjugate covalent organic framework, a preparation method thereof and application of the full-conjugate covalent organic framework in a memristor, and belongs to the field of materials. The fully-conjugated covalent organic framework is prepared by reacting a terephthalaldehyde derived structure BMBA (2, 5-bis (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborol-2-yl) terephthalaldehyde) with TA (2, 4, 6-tri (hydrazino)-1, 3, 5-triazine) under the condition of a liquid-liquid interface, and the fully-conjugated covalent organic framework is prepared by reacting the BMBA (2, 5-bis (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborol-2-yl) terephthalaldehyde) with TA (2, 4, 6-tri (hydrazino)-1, 3, 5-triazine). The prepared DAB-COF film has the characteristics of high structural order, high pi-full conjugation degree, clear charge transfer channel and the like, is used as a memristor functional layer for the first time, and shows excellent resistive storage performance.

The invention relates to proximity activated cytokine compounds comprising a PD-1 targeting moiety, and an IL-21 polypeptide covalently linked to an anti-IL-21 antibody-binding domain, which together provide targeted cytokine signaling to PD-1 expressing cells. The invention further relates to nucleic acid and expression vectors encoding proximity activated cytokines, as well as use of such compounds for treating cancer.

The invention belongs to the field of analytical chemistry, relates to material preparation, and particularly discloses a preparation method of a copper-doped covalent organic framework and application of the copper-doped covalent organic framework in adrenaline colorimetric detection. Firstly, 1H-indazole-4, 7-diamine (Iz) and 1, 3, 5-triformyl phloroglucinol (Tp) are used as monomers to synthesize a novel covalent organic framework (Iz-Tp COF) through a Schiff base reaction, copper ions are introduced into the Iz-Tp COF framework to prepare a novel metal covalent organic framework (Iz-Tp (at) Cu), and then according to the phenomenon that the Iz-Tp (at) Cu can catalyze oxidation color development of epinephrine, the metal covalent organic framework (Iz-Tp (at) Cu can catalyze oxidation color development of epinephrine. According to the present invention, the simple, sensitive and efficient adrenaline colorimetric detection method is established, the test conditions are finally optimized, the standard addition method is combined to accurately determine the adrenaline concentration in the urine, and the good practical application value is provided.

The invention relates to a high-water-solubility denitroflavin covalent complex as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis and medicinal chemistry. Comprising the following steps: (1) firstly, carrying out bromination reaction on 3-methyl-10-ethyl denitroflavin, so as to obtain 3-methyl-10-(1-bromoethyl) denitroflavin; and (2) coupling the 3-methyl-10-(1-bromoethyl) denitroflavin with vitamin C, so as to obtain the high-water-solubility denitroflavin covalent complex. According to the present invention, the prepared highly water-soluble denitrificin covalent complex has the two-phase solubility of the organic solvent and the water, such that the water solubility of the 3-methyl-10-ethyl-denitrificin is substantially enhanced, and the application range of the denitrificin is expanded. And meanwhile, the denitrified flavin covalent compound also has good antioxidant activity, and the antioxidant duration can be prolonged.

The invention discloses an environment-friendly bio-based coated controlled-release fertilizer with multiple enzymolysis targets and a preparation method of the environment-friendly bio-based coated controlled-release fertilizer, and belongs to the technical field of controlled-release fertilizer production. The environment-friendly bio-based coated controlled-release fertilizer comprises a fertilizer core, an enzyme trigger type internal response layer and a pH sensitive trigger type outer layer, the enzyme trigger type internal response layer is prepared from cationic hydroxyethyl cellulose polyester polyol, an enzyme active site targeting modifier and a degradation accelerator; the pH sensitive trigger type outer layer is prepared from cationic hydroxyethyl cellulose polyester polyol and a covalent self-adaptive network modifier; the outer coating of the fertilizer disclosed by the invention can be degraded under the momentary excitation that the pH value in the coating is reduced after nutrients are released, and can promote degradation microorganisms in soil to be adsorbed to the enzyme-triggered internal response layer, so that the degradation of the internal coating is accelerated. The pH sensitive trigger type outer layer has a promoting effect on the enzyme trigger type inner response layer, and the promoting effect is enhanced by adding the degradation accelerator.

The invention discloses an anti-tumor drug delivery system based on click chemistry and a hollow covalent organic framework material as well as a preparation method and application of the anti-tumor drug delivery system, and belongs to the technical field of novel biomedical materials. The anti-tumor drug delivery system based on the click chemistry and the hollow covalent organic framework material comprises a bowl-shaped hollow covalent organic framework material carrier, and a click chemistry prodrug 1 and a click chemistry prodrug 2 which are loaded in the bowl-shaped hollow covalent organic framework material carrier, the click chemistry prodrug 1 is a compound containing an aldehyde group, and the click chemistry prodrug 2 is a compound containing an amino group. By combining the high-specificity reaction of click chemistry with the excellent drug loading performance of HCOF, accurate drug release can be realized in a tumor-specific microenvironment, the toxicity of normal cells can be remarkably reduced, the treatment effect is improved, and a wide clinical application prospect is shown.

The invention discloses an ROS-responsive prostate cancer targeting prodrug as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The prodrug is formed by covalently linking a prostate cancer targeting peptide SYEELR, a ROS (reactive oxygen species) response type ketal thiol (TK) connexon and an active molecule Devimistat. The preparation method comprises the following two steps: firstly, coupling Devimistat with a TK linker to obtain an intermediate Dev-TK, and then coupling the intermediate Dev-TK with an SYEELR peptide fragment to obtain a target product. The prodrug can specifically break and release Devimistat in a tumor high active oxygen microenvironment, and active targeting delivery is realized by virtue of the SYEELR peptide. The invention provides a novel prostatic cancer treatment strategy with accurate targeting, controllable release, enhanced curative effect and toxicity reduction potential.

The invention discloses a covalent organic framework material based on a boric acid structure, a preparation method of the covalent organic framework material and application of the covalent organic framework material in dopamine detection, and relates to a covalent organic framework material and a preparation method and application of the covalent organic framework material. The technical problems that an existing dopamine recognition method is high in detection limit and harsh in recognition environment are solved. The periodic structure fragment of the covalent organic framework material based on the boric acid structure is shown in the specification. The 2-(4-boric acid phenyl)-5, 10-dinitro-1H-phenanthro [9, 10-d] imidazole diamine and 4, 4 ', 4', 4 ''-(pyrene-1, 3, 6, 8-tetrayl) tetrabenzaldehyde are subjected to a reaction to obtain the 2-(4-boric acid phenyl)-5, 10-dinitro-1H-phenanthro [9, 10-d] imidazole diamine derivative. The covalent organic framework material based on the boric acid structure is used for detecting dopamine, has relatively high selectivity and anti-interference capability, and is not interfered by amino acid in the environment. And the covalent organic framework material based on the boric acid structure can be embedded in the hydrogel, so that the hydrogel is convenient to carry. The method can be applied to detection of dopamine in environment and biological systems.

The invention belongs to the technical field of active polypeptides and preparation, and particularly relates to an antioxidant and anti-inflammatory cyclopeptide capable of inhibiting matrix metalloproteinase as well as a preparation method and application of the antioxidant and anti-inflammatory cyclopeptide. The cyclic peptide is formed by end-to-end covalent coupling of linear peptide with the amino acid sequence of DEETGEF, has the activity of resisting oxidation, resisting inflammation and inhibiting matrix metalloproteinase, is free of cytotoxicity and skin irritation, and is suitable for being used as cosmetics for resisting skin aging, wrinkles and the like.

Provided are covalent organic frameworks (COFs). Also provided are methods of making the COFs and methods of using the COFs. The COF sheets define a plurality of pores, and stack in an eclipsed configuration to form sheets that assemble to form nanoparticles. Each COF sheet may be a co-condensate of p-phenylenediamine (PA) and (i) triformylbenzene (TFB) and triformylphloroglucinol (TP) or (ii) triformylphloroglucinol (TP). A COF of the present disclosure has the following structure: Formula (I) and / or Formula II where each X2 is Formula (III) where earch X1 is Formula (IV) Formula (V) Formula (VI) Formula (VII) Formula (VIII) Formula (IX) Formula (X) Formula (XI) Formula (XII) Formula (XIII) or any tautomer thereof, where at least one X1 is not Formula (XIV).

The invention relates to an enzyme response antibacterial carbon dot and a preparation method and application thereof.The carbon dot takes a copper-doped carbon dot as a core and is covalently grafted with a hyaluronic acid shell layer through amidation reaction to form a composite nano material Cu-CDs (at) HA, specifically, soluble copper salt and folic acid are subjected to a hydrothermal reaction to obtain the copper-doped carbon dot, carboxyl is activated through EDC / NHS in a buffer system, and the carbon dot is prepared. And performing grafting reaction with hyaluronic acid to obtain a target product. The hyaluronidase-containing antibacterial composition can be specifically degraded and release antibacterial components under the action of hyaluronidase, shows good bacterial responsive bactericidal performance, has the minimum inhibitory concentrations of 8 g / mL and 16 g / mL for staphylococcus aureus and escherichia coli respectively, and has peroxidase-like activity and free radical scavenging capacity. The antibacterial carbon dots can be used for preparing intelligent wound dressings, antibacterial coatings and other biomedical materials, and have the advantages of responsive drug release, efficient antibacterial property and promotion of wound repair.

The present application relates to a kind of phosphine oxy group covalent modification composite adsorption material and its preparation method and purposes, the preparation method includes the following steps: (1) mixing dopamine hydrochloride, phosphine-containing substrate, tris-hydroxymethyl aminomethane hydrochloride and sodium hydroxide in solvent, to obtain mixed solution;(2) the mixed solution obtained in step (1) and solid phase material are mixed, then oscillation reaction is carried out, to obtain solid-liquid mixture;(3) the solid-liquid mixture obtained in step (2) is carried out solid-liquid separation, and the solid phase part obtained is sequentially washed and dried, to obtain phosphine oxy group covalent modification composite adsorption material.The phosphine oxy group covalent modification composite adsorption material provided by the present application has excellent adsorption selectivity and material stability, and can be used for the high-selectivity separation and recovery of rare metals indium and gallium.