3182 results about "Covalent modifier" patented technology

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.

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.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes (e.g., wherein each complex is of the exemplary formula shown below) comprising a phosphorodiamidate morpholino oligomer (e.g., useful for targeting DMD) covalently linked to an antibody (e.g., anti-TfR1 antibody). In some embodiments, the complexes are formulated with histidine (e.g., L-histidine) and sucrose at a specified pH (e.g., about 5.0 to 7.0). Also provided are uses of these formulations for treating a subject having a mutated DMD allele associated with Duchenne Muscular Dystrophy.

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.

Compounds that are covalent inhibitors of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2); compositions comprising same; and their use for treating cancers.

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 belongs to the technical field of separation membrane materials, and provides a covalent organic framework membrane as well as a preparation method and application thereof. The preparation method comprises the following steps: preparing an organic phase solution containing a polyaldehyde monomer and a water phase solution containing a polyamine monomer; dropwise adding the organic phase solution to the aqueous phase solution for reaction, and dialyzing the solution after the reaction is finished to obtain a purified aqueous dispersion of the covalent organic framework nanosheet; and dispersing the aqueous dispersion, carrying out suction filtration to a hydrophilic support, and carrying out heat treatment and curing. The invention also discloses the covalent organic framework membrane prepared according to the method and application thereof. The covalent organic framework membrane is used for removing divalent ions in a saline solution. The covalent organic framework membrane disclosed by the invention has an ordered pore structure with a specific size and high ion selectivity; due to the strong covalent bond connection characteristic, the covalent organic framework film is endowed with acid and alkali resistance and high stability; the preparation method disclosed by the invention is simple, mild in condition and wide in application range.

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.

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 an acylhydrazone bond-linked three-component covalent organic framework material and application thereof in photocatalytic full-decomposition of water. The three-component COFs expands the designability of the structure and function of the porous organic material by generating ordered anisotropic tiling and ordered pores with abnormal shapes. In addition, COFs connected through acylhydrazone bonds have good thermal stability and chemical stability, and nitrogen atoms on the acylhydrazone bonds can provide a large number of sites for load metal. According to the invention, two electron-deficient and electron-rich nodes are introduced into a COFs framework to form a donor-pi-acceptor structure motif, and Pt metal nanoparticles are loaded onto a three-component covalent organic framework material by using a NaBH4 reduction method. The material has great potential in the aspect of producing H2 and H2O2 through photocatalytic full decomposition of water by taking water as a reactant while solar energy is utilized and a sacrificial agent is not added.

The invention belongs to the field of nano-drug preparations, and discloses a multifunctional nano-enzyme platform and a preparation method and application thereof, and the multifunctional nano-enzyme platform is mainly composed of a nano-enzyme, a carrier material and a targeting substance. The synthesis of the nano-enzyme, the loading of the nano-enzyme on a carrier material and the modification of a targeting substance on the surface of the nano-enzyme are carried out through methods such as stirring synthesis, coprecipitation, strong acid oxidation, chemical reduction, covalent binding, a solvothermal method and physical adsorption. The targeting substance on the surface of the nano-enzyme platform can be accurately and efficiently positioned to an inflammation part, the meta-acid microenvironment of the inflammation part enables the targeting substance and the carrier material to be subjected to structural depolymerization, so that various nano-enzymes are released, and the nano-enzymes not only realize self-cascade and synergistic catalysis enhancement effects of the enzymes at the inflammation part, but also can be used for preparing the nano-enzyme. And a substrate self-circulation catalysis system is also formed, so that the effect of efficiently relieving and treating various inflammation-related diseases is achieved.

The invention belongs to the technical field of biological medicines, and particularly discloses an epidermal growth factor-linker polypeptide-collagen, and the linker polypeptide has an amino acid sequence as shown in SEQ ID No.1. The linker polypeptide capable of connecting the EGF and the collagen is designed and synthesized, the N end of the linker polypeptide simulates an EGF receptor structure and can be combined with the EGF, and the linker polypeptide is connected with the EGF through non-covalent Van der Waals force, so that the structure of the EGF cannot be damaged; the C terminal of the linker polypeptide is rich in lysine residues, and can be covalently crosslinked to collagen through glutamine transaminase to form EGF-linker polypeptide-collagen. The protein solution taking EGF-linker polypeptide-collagen as active ingredients is low in cytotoxicity and high in biological safety, and meanwhile, the action time of the epidermal growth factor can be remarkably prolonged. In addition, a stable repairing microenvironment can be formed on the surface of the endometrium, and the endometrium injury repairing effect is remarkably improved.

The invention discloses a preparation method and application of a ternary multifunctional three-dimensional framework mediated high ammonia nitrogen selectivity polyamide reverse osmosis membrane, and belongs to the technical field of membrane separation. The method comprises the following steps: 1, preparing a high-molecular copolymer; 2, preparing a polysulfone support layer by adopting a non-solvent induced phase inversion method; 3, preparing a polyamide reverse osmosis membrane by adopting an interfacial polymerization method; and 4, preparing the polyamide reverse osmosis membrane with high ammonia nitrogen selectivity. Through reasonable design of the structure and distribution of the group of the ternary multifunctional three-dimensional structure high-molecular copolymer, the copolymer can react with the acyl chloride group on the surface of the polyamide active layer to form a covalent amido bond, and the covalent amido bond is anchored on the surface of the polyamide layer in situ to construct the functional layer. The functional layer not only can significantly improve the surface potential of the membrane, but also can increase the inherent concentration of ammonia nitrogen on the surface of the membrane, thereby increasing the diffusion resistance, finally realizing the repulsive force to the ammonia nitrogen, and improving the interception capability of the grafted membrane to the ammonia nitrogen. The operation process is simple and mild, the whole membrane preparation process is not changed, and industrialization is easy.

The invention relates to a dynamic-covalent hybrid cross-linked hydrogel material as well as a preparation method and application thereof. The preparation method comprises the following steps: dissolving a component A-phenylboronic acid modified polymer derivative in a biocompatible medium to obtain a solution A; dissolving a component B, namely a macromolecular derivative containing a vicinal diol group, into a biocompatible medium to obtain a solution B; dissolving a component C-double bond group modified polymer derivative in a biocompatible medium to obtain a solution C; and mixing the solution A, the solution B and the solution C with certain concentrations for a certain time, and performing illumination under a photoinitiator for a certain time to obtain the dynamic-covalent hybrid cross-linked hydrogel material. Compared with single dynamic bond crosslinking or covalent bond crosslinking, the prepared hydrogel material has machinability and mechanical stability; the hydrogel material has plasticity, shear thinning, self-repairing property and the like in the early stage of crosslinking; enough mechanical strength and long-term stability are realized in the later stage of crosslinking.

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 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.

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.

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.

β-Ketoenamine covalent organic frameworks (COFs) provide remarkable water sorption capabilities and stable adsorption–desorption cycling, particularly under low relative humidity (RH) conditions.

The phosphazene covalent organic framework (COF) is a material with high efficiency to improve the removal of iodine from nuclear waste. The COF can be obtained by a solvothermal reaction of hexa(4-formyl-phenoxy)cyclotriphosphazene and 1,3,6,8-tetra(aminophenyl)pyrene. The resulting three-dimensional phosphazene COF has iodine uptakes as high as 9.4 g g−1 due to its 3D framework with higher specific surface areas and interconnected channels.

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 preparation method of a high-activity hierarchical pore boric acid imprinted hydrogel microsphere adsorbent and application of the adsorbent to selective adsorption of a flavonoid compound naringin NRG. According to the invention, dopamine is used for modifying COFs so as to enhance surface functionalization of COFs; preparing a sulfydryl functionalized covalent organic framework microsphere; synthesizing sulfydryl microspheres by utilizing an emulsion interfacial polymerization method; preparing a COFs boron affinity imprinting microsphere adsorbent based on boron affinity interaction; the adsorbent is applied to selective adsorption of NRG in agricultural wastewater. The prepared adsorbent has a remarkable multilayer adsorption effect, and the adsorption capacity is remarkably improved through the boron affinity effect. The multi-stage pore structure of the COFs microspheres provides abundant sites for adsorption, and the mass transfer rate is remarkably improved. In addition, the prepared adsorbent shows remarkable specificity in the aspects of adsorption and separation of NRG, and a promising adsorption material is provided for industrial separation of NRG.

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 discloses hyaluronic acid / alginic acid dual-network hydrogel as well as a preparation method and application thereof. The hyaluronic acid / alginic acid double-network hydrogel comprises a first network and a second network which are not crosslinked with each other, and the first network and the second network are distributed in the hydrogel in an interpenetrating manner; the first network comprises an ionic cross-linked network of alginic acid with cell adhesion sites and calcium ions, and the second network comprises a chemical cross-linked network formed by covalent cross-linking of methacrylic anhydride modified hyaluronic acid. The hyaluronic acid / alginic acid double-network hydrogel disclosed by the invention is short in curing time, supports three-dimensional spreading of cells and formation of capillary lumens, has good mechanical stability, and has good application prospects in the aspects of three-dimensional culture of the cells, tissue engineering construction and the like.

The invention discloses a method for preparing a high internal phase emulsion and delivering curcumin by using transglutaminase mediated casein-carboxymethyl chitosan covalent substances, aims to improve the stability and bioaccessibility of curcumin, and belongs to the field of food processing. The method comprises the following steps: firstly, carrying out ultrasonic treatment on sodium caseinate for a certain time, and carrying out transglutaminase cross-linking reaction on sodium caseinate and carboxymethyl chitosan to obtain a casein-carboxymethyl chitosan covalent substance; and then adding the mixture into the curcumin-loaded corn oil according to a certain proportion, and homogenizing to obtain the curcumin-loaded high internal phase emulsion. The emulsion has good interface characteristics and can effectively encapsulate curcumin. The preparation process is simple, efficient, green and environmentally friendly, the prepared high internal phase emulsion has high stability and good biological accessibility, a new technical means is provided for delivery of curcumin, and the high internal phase emulsion has wide application prospects in the field of food.

The invention belongs to the technical field of biomedical materials, and particularly relates to an anti-inflammatory nano drug delivery system containing a guanidyl structure as well as a preparation method and application of the anti-inflammatory nano drug delivery system, the anti-inflammatory nano drug delivery system is B (at) COFDT-R obtained by taking COFDT as a carrier, loading a drug and then wrapping the drug with an erythrocyte membrane, and the COFDT is obtained by taking DG and TP as raw materials in a reaction of mesitylene / 1, 2, 4-trimethylbenzene / 1, 2, 4-trimethylbenzene / 1, 2, 4-trimethylbenzene / 1, 2, 4-trimethylbenzene / 1, 2, 4-trimethylbenzene and carrying out a high-temperature microwave reaction in a 1, 4-dioxane / acetic acid system. The anti-inflammatory nano drug delivery system disclosed by the invention takes a covalent organic framework material as a carrier platform, and integrates the babarid into a COFDT cavity, so that neuronal cells are protected by inhibiting neuroinflammation and pyroptosis of neurons after subarachnoid hemorrhage.

The disclosure provides interleukin 21 (IL-21) variants that have (i) decreased or no binding to a human interleukin 21 receptor (IL-21R) as compared to a wild-type human IL-21 polypeptide; or (ii) increased stability as compared to a wild-type human IL-21 polypeptide; or (iii) decreased or no binding to a human interleukin 21 receptor (IL-21R) as compared to a wild-type human IL-21 polypeptide and increased stability as compared to a wild-type human IL-21 polypeptide. The disclosure also provides fusion proteins including an antibody or fragment thereof bound, e.g., covalently linked, to an IL-21 variant.

The present invention relates to magnetic, catalytically active, and radiosensitizing nanoparticles (NanoXcats) and the method for their production. A method is disclosed for the production of functionalized greigite nanoparticles with a narrowband size distribution (10-30 nm) for use in multimodal cancer therapy. NanoXcats are superparamagnetic Fe3S4 nanoparticles whose surfaces are equipped with polar functional groups. The surface structures of NanoXcats are suitable for conjugation with, or for covalent or electrostatic binding of, active substances, which may be cancer drugs, cell growth inhibitors, or NO donors. Due to the EPR effect, NanoXcats are preferentially internalized by tumor cells. The targeted accumulation of NanoXcats in tumor tissue is achieved by an external inhomogeneous magnetic field. NanoXcats exhibit enhanced catalytic activity in tumor cells.The catalytic activity of intracellular NanoXcats can be triggered, controlled, and enhanced by low-dose X-rays. Surface-bound drugs are additionally activated in tumor cells by the catalytic activity of NanoXcats. NanoXcats act as superoxide dismutase, nitric oxide synthase, and Fenton catalyst. They catalyze, for example, reactions of the superoxide anion radical to hydrogen peroxide, of L-arginine to NO, and of hydrogen peroxide to the hydroxyl radical.

The invention discloses high-stability immobilized candida antarctica lipase B as well as a preparation method and application thereof, and belongs to the technical field of enzyme engineering and biological catalysis. The preparation method comprises the following steps: modifying resin by adopting a silane coupling agent to obtain silanized resin; carrying out aldehyde functional modification on the silanized resin by using dialdehyde cellulose to obtain alkyl-aldehyde modified resin; candida antarctica lipase B is immobilized by using alkyl-aldehyde modified resin, and after the Candida antarctica lipase B is subjected to interfacial activation on the surface of the alkyl-aldehyde modified resin, the Candida antarctica lipase B is covalently bound with aldehyde on the surface of the alkyl-aldehyde modified resin; the prepared immobilized Candida antarctica lipase B has relatively high activity and stability. The method is simple to operate, the prepared immobilized lipase is high in stability, and the method can be used for preparing the high-stability immobilized lipase on a large scale and has the potential of industrial popularization and application.