308 results about "Covalent binding" patented technology

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 relates to the technical field of preparation of antibacterial gloves, in particular to a preparation method of degradable breathable antibacterial gloves, and an emulsion formula of the degradable breathable antibacterial gloves comprises the following components in parts by weight: 100 parts of nitrile rubber modified polylactic acid, 5-10 parts of modified antibacterial filler, 1-3 parts of an anti-aging agent, 0.5-3 parts of a vulcanizing agent, 0.3-2 parts of a vulcanization accelerator and 0.5-1 part of a foaming agent. Through a high-molecular compound composition system, nitrile rubber modified polylactic acid, modified antibacterial filler and other components are compounded to prepare the glove with controllable degradability, lasting antibacterial property and good air permeability; on the basis of covalent binding of silicon dioxide loaded with antibacterial groups and modified chitosan, the synergistic antibacterial effect of the modified antibacterial filler is achieved, and therefore the antibacterial performance of the glove is improved.

A nanoparticle complex comprises a bifunctional binder capable of non-covalently binding to the lipid nanoparticle in the nanoparticle complex.

The invention discloses a beta-lactoglobulin modified near-infrared fluorescent targeting probe as well as a preparation method and application thereof. The probe comprises indocyanine green (ICG) and beta-lactoglobulin (beta-LG) which are covalently bound. Compared with the prior art, the probe disclosed by the invention has the advantages that (1) the probe disclosed by the invention improves the stability of the near-infrared fluorescent dye in a body and prolongs the retention time of the near-infrared fluorescent dye, so that the observation window time is prolonged, imaging information is fully acquired in real time, and the effective circulation time in the body is prolonged; (2) the probe has the advantages of good biocompatibility, low toxicity and the like; and (3) the probe can specifically enrich in renal tubules and perform targeted imaging in kidneys, so that diagnosis and treatment of kidney injury, especially acute injury, are realized.

The invention provides a drug permeability clinical prediction model, a construction method thereof and a non-specific drug permeability evaluation method, and belongs to the technical field of biological medicine. The invention provides a construction method of a drug permeability clinical prediction model. According to the construction method, intestinal microorganism characteristics are introduced into model construction for the first time. The prediction performance of the constructed LGBM model containing the intestinal microorganism characteristics in the aspect of NAC permeability prediction is superior to that of other traditional business models. The invention also provides a serine-derived sphingolipid de novo synthesis pathway, which is different from the traditional sphingolipid de novo synthesis pathway, and is named as a cysteine sphingolipid metabolism pathway, NAC-derived cysteine may participate in the biosynthesis of microbial sphingolipid through covalent binding with palmitoyl-CoA, thereby damaging intestinal permeation of NAC.

The invention discloses a gastrodia elata polypeptide extraction process, and belongs to the technical field of polypeptide extraction. According to the method, gastrodia elata cell membranes are broken through acetone pretreatment, so that protein and lipid are dissociated, trimethylsilyl ether passivates active groups, immobilized enzyme decomposes cellulose and adipose tissues through normal-temperature enzymolysis, a protein stabilizer prevents oxidation and inhibits enzyme activity, differential pressure extraction is combined with a sodium pyrophosphate buffer solution, polypeptide is promoted to be dissolved out, and activity is maintained; the high extraction rate of the gastrodia elata polypeptide and low-active group destructiveness are realized. Reaction sites and binding force are increased by epoxy groups on the surface of an immobilized enzyme carrier prepared by modifying corn starch, enzyme molecules are stable and appropriate due to good biocompatibility, enzyme molecule conformation is optimized through covalent binding, a rigid structure is enhanced, enzyme activity is kept at a high level for a long time, continuous and efficient enzymolysis is performed in gastrodia elata polypeptide extraction, and the gastrodia elata polypeptide extraction efficiency is improved. Compared with the traditional free enzyme, the gastrodia elata polypeptide enzyme has the advantages that the enzyme use cost is reduced, the enzyme consumption and waste generation are reduced, and an efficient and economical scheme is provided for gastrodia elata polypeptide extraction.

The invention discloses a method for enriching a sulfydryl-containing peptide fragment based on covalent binding, in the method, a chemical reagent, namely 2-(2-pyridyl disulfide) ethylamine, capable of reacting with sulfydryl is used, the reagent comprises two functional reactive groups, specifically, amino and pyridyl disulfide, the amino can react with carboxyl magnetic beads, and the sulfydryl-containing peptide fragment can react with carboxyl magnetic beads. A novel pyridine disulfide-based magnetic bead material, namely the pyridine disulfide-based agar magnetic bead, is formed. According to the method, pyridine disulfide can directly react with the sulfydryl peptide fragment to form a covalent bond, so that the enrichment of the sulfydryl peptide fragment is realized, the sulfydryl peptide fragment can be eluted by adding a reducing agent such as DTT, and the method has the characteristics of low cost, good selectivity and the like.

The invention discloses a chitosan-casein peptide nano-particle and a preparation method and application thereof, and belongs to the technical field of food manufacturing, chitosan and casein peptide are combined into a nano-composite with the particle size of 10-1000 nm through electrostatic interaction in a non-covalent binding mode, and the nano-composite is used for preparing the chitosan-casein peptide nano-particle. A more stable oil-in-water emulsion can be prepared by utilizing the nano composite; the invention also provides a preparation method and application of the chitosan-casein peptide nanocomposite, and a preparation method of the oil-in-water emulsion. The nano-composite prepared by the invention has relatively strong oxidation resistance, foamability and foaming stability when the ratio of chitosan to casein peptide is 1: 1, and an oil-in-water emulsion prepared from the nano-composite has good storage stability, pH stability and ion stability. The preparation method of the nanocomposite is simple and low in cost, and has a good application prospect.

The invention relates to the technical field of biomedicine, in particular to a cross-linked modified artificial valve and a preparation method and application thereof. The preparation method comprises the following steps: firstly, preparing a novel compound POSS-PEG-NHS, and carrying out esterification reaction on a-NHS group of the compound and a-NH2 group on the surface of the decellularized porcine valve to realize covalent binding; then, an inherent reducing agent glutathione in an organism is added, and the cross-linked modified artificial valve PPN-GSH-AV is obtained. The valve shows excellent cell safety and blood compatibility, and has obvious advantages compared with a traditional glutaraldehyde cross-linked valve. In-vivo experiments show that the PPN-GSH-AV has high biological safety and histocompatibility, and can effectively reduce immunological rejection. In addition, the valve can relieve oxidative stress of macrophages and promote M2 type transformation, so that inflammatory response is relieved. In clinical application, the PPN-GSH-AV shows a good anti-inflammatory effect and excellent anti-calcification performance, in-vitro pulsating flow test results meet international standards, and the PPN-GSH-AV has clinical transformation potential and wide application prospects.

An improved polyurea and chitosan core-shell delivery particle that encapsulates a benefit agent is described. Chitosan is pre-modified with a modifying compound, which is cationic, anionic or nonionic. Alternatively, modification is completed in situ. The modifying compound is selected from the group consisting of epoxides, aldehydes or alpha, beta-unsaturated compounds and reacts with the free amine moiety of the chitosan, covalently bound to the amine moiety of the chitosan via a CN bond. The modifying compound may contain an acidic group, a hydroxyl group, and a quaternary ammonium group. The reaction product of chitosan, a modifying compound, and an electrophile, preferably a polyisocyanate, produces microcapsules that have charge, improved release properties, improved compatibility, or enhanced degradation properties (e.g., in OECD Test Method 301B).

The invention belongs to the technical field of immunochemiluminescence, and relates to a PAMAM-mediated labeled small molecule compound and a synthesis method and application thereof.The PAMAM-mediated labeled small molecule compound is composed of small molecules, PAMAM and a marker, and the small molecules are provided with active groups or provided with derivative groups capable of reacting with amino under certain activation conditions to form covalent binding; the marker is provided with a succinimide group. The difference between a coupling product and a small molecular structure is reduced to the maximum extent through PAMAM mediation, the PAMAM dosage is extremely small and stable, compared with PEG, the molecular weight is more uniform, non-specific binding caused by hydrophobic interaction can be greatly reduced in immunoreaction, and good signals and separation can be obtained without purification of the product.

The invention discloses a multifunctional tumor targeted low-temperature treatment nano platform and application thereof, and belongs to the technical field of nano biological medicines. According to the multifunctional tumor targeted low-temperature treatment nano platform, the two-dimensional Ti3C2 nano material serves as a carrier, indocyanine green is loaded to serve as a photosensitizer, polydopamine is modified on the surface to improve the stability, and gambogic acid is loaded to serve as an anti-tumor drug and a heat shock protein inhibitor; and a nucleic acid aptamer capable of recognizing specific protein on the cell surface is coupled in a covalent binding manner. The multifunctional tumor targeted low-temperature treatment nano platform is small in particle size, high in dispersion degree and good in biocompatibility, and shows excellent photo-thermal conversion capacity, photodynamic treatment effect and chemotherapy effect in tumor targeted treatment. The apoptosis of tumor cells can be effectively induced under a relatively low temperature condition, and the damage of high temperature to surrounding healthy tissues is remarkably reduced. The tumor focus specific recognition capability is also realized, the high enrichment at the tumor part can be realized, and the treatment effect is enhanced.

The invention relates to the technical field of enzyme catalysis, relates to the technical field of bioengineering application, and in particular relates to a magnetic nitrilase catalyst for green cyclic synthesis of organic acid as well as a preparation method and application of the magnetic nitrilase catalyst. According to the method, nitrilase escherichia coli is fixed on a magnetic composite carrier in a covalent binding and adsorption-crosslinking manner to form a magnetic nitrilase catalyst, and the catalyst is used for catalytic synthesis of organic acid; after the reaction is finished, the magnetic nitrilase catalyst is recovered by magnetic attraction, and the reaction waste liquid is acidized to realize the purpose of green cyclic synthesis of the organic acid. The prepared magnetic nitrilase catalyst can stably exist in nitrile substances and has the advantages of being high in mechanical strength, low in enzyme activity loss rate and easy to store, the magnetic nitrilase catalyst and reaction liquid can be recycled, beneficial reference is provided for promoting clean, environment-friendly and efficient enzyme method production of organic acid, and the application prospect is wide. The method has huge application potential in continuous separation and industrial application.

The present invention relates to a compound binding to an endogenous receptor, said compound comprising (i) an oligopeptide comprising a dipeptide with Trp being the C-terminal amino acid of said dipeptide, wherein said Trp is replaced with an α-amino acid Xaa2, whereby the stability in serum or plasma of the peptide bond connecting Xaa2 to the N-terminally adjacent amino acid is increased as compared to the peptide bond connecting Trp to the N-terminally adjacent amino acid in an otherwise identical compound; and (ii) a moiety capable of generating therapeutically effective radiation, said moiety being covalently bound to said oligopeptide.

The invention discloses application of salvianolic acid A in preparation of a medicine for preventing and treating vulnerable plaques of advanced atherosclerosis. The invention also discloses application of the salvianolic acid A combined with ferulic acid or the salt thereof in preparation of drugs for preventing and treating advanced atherosclerosis vulnerable plaques. Researches find that salvianolic acid A can promote apoptosis of senescent vascular smooth muscle cells and has a Senlytics effect; the salvianolic acid A stabilizes vulnerable atherosclerotic plaques by reducing the load of senescent vascular smooth muscle cells; the salvianolic acid A is in non-covalent binding with ASP54, ALA55, LYS58, ASP93, ASP102 and LYS112 of the HSP90AA1 to play a role in inhibition, and the ASP93 has the greatest contribution to binding free energy. The research of the invention is of great significance to the development and application of drugs with anti-aging effect for stabilizing advanced atherosclerotic vulnerable plaques.

Provided are polymer compositions made by a process comprising: (a) providing a first reactive composition containing: (i) a polymerization initiator that is capable, upon a first activation, of forming two or more free radical groups, at least one of which is further activatable by subsequent activation; (ii) one or more ethylenically unsaturated compounds; and (iii) a crosslinker; (b) subjecting the first reactive composition to a first activation step such that the first reactive composition polymerizes therein to form a crosslinked substrate network containing a covalently bound activatable free radical initiator; (c) contacting the crosslinked substrate network with a grafting composition containing one or more ethylenically unsaturated compounds, wherein the contacting is conducted under conditions such that the grafting composition penetrates into the crosslinked substrate network; and (d) activating the covalently bound activatable free radical initiator at one or more selective regions of the crosslinked substrate network such that the grafting composition polymerizes with the crosslinked substrate network at the selective regions.

The invention discloses an electrochemical biosensor for detecting mycobacterium tuberculosis. The sensor takes a porous membrane as a base material, the inner wall of a pore channel of the porous membrane is co-modified with a polydopamine (PDA) and conductive carbon material composite layer, and an amino-modified specific capture probe based on a mycobacterium tuberculosis ESAT-6 gene is fixed on a modification layer through covalent binding. When a target gene is captured by a probe, the volume effect of the target gene causes blockage of a porous channel of the porous membrane, so that electrochemical signals (such as current) of the sensor are changed, and high-sensitivity and specific detection of mycobacterium tuberculosis is realized. According to the invention, a porous structure, biological probe specific fixation and an electrochemical signal conversion technology are combined, and a novel efficient tool is provided for rapid diagnosis of tuberculosis.

The invention discloses an amphiphilic sizing agent suitable for a glass fiber / resin composite material, which is prepared by polymerizing glycidyl methacrylate and methacrylic acid ethyl trimethyl ammonium chloride by a reversible addition-fragmentation chain transfer polymerization method to form glycidyl ester-ethyl trimethyl ammonium chloride; and introducing dopamine methacrylamide by using a free radical polymerization technology to obtain the amphiphilic sizing agent. The amphiphilic sizing agent can be applied to the surface of the glass fiber without being filled with a plasticizer, a coupling agent, an inhibitor and the like, the coating performance and the binding performance of a product can be adjusted by changing the proportion of structural units, and the amphiphilic sizing agent can form a covalent binding effect with hydroxyl on the glass fiber through epoxy; positive charges and negative charges on the surface of the glass fiber can form electrostatic interaction combination, and dopamine groups and groups on the resin can form powerful hydrogen-bond interaction, so that efficient load transfer is realized.

The present invention belongs to the field of nano drug preparations, and discloses a multifunctional nanozyme platform and its preparation method and application, which is mainly composed of nanozymes, carrier materials and targeting substances. The synthesis of nanozymes, the loading of nanozymes on carrier materials and the modification of their surface targeting substances are carried out by methods such as stirring synthesis, coprecipitation, strong acid oxidation, chemical reduction, covalent bonding, solvent thermal method, physical adsorption, etc. The targeting substance on the surface of the nanozyme platform can be accurately and efficiently positioned to the inflammation site, and the acidic microenvironment of the inflammation site causes the targeting substance and the carrier material to undergo structural depolymerization, thereby releasing a variety of nanozymes, which not only realize the self-cascade and synergistic catalytic enhancement of enzymes at the inflammation site, but also form a substrate self-circulation catalytic system, thereby achieving the effect of efficiently alleviating and treating various inflammation-related diseases.

A precursor compound and a radioligand for cancer diagnosis and treatment comprises a high-affinity ligand PL for a cancer- associated protein conjugated to a covalent warhead CW for strong or covalent binding to an amino acid sidechain of the cancer-associated protein and a chelator Ch for complexation of a radioisotope or a leaving group LR for substitution with a radioisotope, wherein the covalent warhead CW is configured for quasi-covalent ionic binding using a sulfonic acid group or for covalent binding using a sulfur fluoride exchange (SuFEx) group, a benzotriazole or N-methyl-N- arylmethanesulfonamide leaving group or a malolactone group for strain-release alkylation.

The invention belongs to the field of biological medicine, and relates to a human serum albumin covalent binding type targeted folate receptor micromolecule drug conjugate prodrug and application thereof. The prodrug disclosed by the invention has a structure as shown in a formula I, six-carbon maleimide is used as a site combined with endogenous albumin, and albumin is used as a carrier to deliver the drug. The prodrug can increase accumulation of the drug in tumors under the EPR effect. A dipeptide chain composed of valine and alanine is used as a cleavage site of cathepsin B, an adapter composed of p-aminobenzyl ether and N-methylamino-4-nitrophenol releases drugs in an acidic environment, an azidohexanoic acid structure is added to a side chain of p-aminobenzyl ether, so that the site of a targeting ligand can be increased, and SN38 is used as a small molecule cytotoxic load. The micromolecular prodrug has dual functions of active targeting and passive targeting, and can effectively improve the concentration in solid tumors, reduce toxic and side effects and improve the anti-tumor effect under the mediation of related receptors.

The invention belongs to the technical field of biological medicines, and particularly relates to a PPV-PCV2 nanoparticle vaccine design and a preparation method. According to the invention, PPV1VP2 protein is used as a skeleton, a SpyTag peptide fragment is inserted into a loop 2 region of the VP2 protein, and the fusion protein is expressed by using an insect cell baculovirus system and is marked as PPV-ST; a plurality of B cell epitopes of Cap protein of PCV2 and a plurality of T cell antigen epitopes of Rep protein of PCV2 are connected in series, a SpyCatcher peptide fragment is fused at an N end, and expression is performed by using a prokaryotic expression system and is marked as SC-PCV2. Finally, the PPV-ST protein and the SC-PCV2 protein are subjected to covalent binding assembly, the nanoparticle vaccine is prepared, and the obtained PPV-PCV2 vaccine has good immunogenicity.

A method for coating a metallic surface by a graphene layer by depositing a graphene molecular precursor comprising a compound having an aromatic hydrocarbon component that is derivatized by a tethering group. The tethering groups react with the metallic surface to form a covalent bond between the compound of the graphene molecular precursor and the non-metallic surface, and the graphene molecular precursor is transformed into a graphene interfacial layer which is covalently bound to the non-metallic surface.

The invention belongs to the technical field of biological medicine, and particularly relates to hyaluronic acid nano-microspheres as well as a preparation method and application thereof. According to the preparation method of the hyaluronic acid nano-microspheres, the hyaluronic acid nano-microspheres are prepared through interaction of nucleic acid, basic amino acid and hyaluronate in a specific proportion, the preparation process is optimized, and the prepared hyaluronic acid nano-microspheres are high in hyaluronic acid adding amount, high in skin permeability and good in skin care effect. The stability is good, and the application requirements in transdermal drug delivery drugs, skin care products and other products are met. Meanwhile, a non-covalent binding mode is adopted for preparing the nano-microspheres, the preparation operation is simple, the gelling property of the hyaluronate is effectively improved, the sticky feeling under high content is improved, and the application scene of hyaluronic acid in the field of skin care products is widened.

The invention discloses a PROTAC chimera for targeted degradation of an ROR [gamma] t receptor and application of the PROTAC chimera, the structure of the chimera is RW-L-Re, Re is a ligand capable of being combined with E3 ubiquitin ligase, L is a linking group covalently combined with at least one Re and at least one RW, and Rw is a target protein ROR [gamma] t binding ligand and is selected from one of the following structures. A series of PROTAC chimeras capable of degrading an ROR gamma t receptor in a targeted manner are designed and synthesized for the first time, a ternary complex is formed mainly by combining a target protein ligand and an E3 ubiquitin ligase ligand with POI and E3 ligase respectively, and then the POI is labeled with a ubiquitination tag and is further degraded by proteasome. Experimental results prove that the PROTAC chimera designed by the invention has excellent ROR [gamma] t receptor degradation activity, and can be used for preparing related drugs for treating autoimmune diseases or tumors.

The invention belongs to the field of environmental biotechnology and nano material application, and relates to a method for accelerating microorganisms to reduce selenite based on immobilized riboflavin. Aiming at the problems of poor stability, difficulty in recovery, non-repeated use and the like of dissolved riboflavin serving as an electron shuttle, riboflavin is grafted on the surface of a multi-walled carbon nanotube through a covalent binding method, and immobilized riboflavin capable of being recycled is constructed. The material can accelerate extracellular electron transfer of shewanella MR-1, and toxic sodium selenite is efficiently reduced into low-toxicity or non-toxic elemental selenium. Results show that the immobilized riboflavin not only maintains high reduction activity of riboflavin, but also has excellent cyclic utilization performance, still maintains high reduction rate after being repeated for multiple times, and effectively reduces operation cost and resource loss. According to the invention, an efficient, economical and sustainable application scene is provided for a microorganism-electron shuttle combined remediation technology, and a new thought is also provided for application of a functional nano material in an environmental biotechnology.

The invention belongs to the technical field of lipase immobilization, and particularly relates to immobilized lipase and a preparation method thereof. The preparation method comprises the following two steps: (I) preparation of activated amino type silica gel resin: mixing amino type silica gel resin, a nonionic surfactant 1308 and deionized water according to a mass ratio of (1000-1100): (2000-2200): (5-8), stirring at 1-5 DEG C for 10-15 minutes, adding cyanuric chloride, dripping a 30-35 wt% sodium hydroxide solution, reacting, and centrifuging; (II) preparation of immobilized lipase: mixing the activated resin, a surfactant, deionized water and a lipase solution, dropwise adding an alkaline solution at 40-45 DEG C under the condition that the pH is 5.0-5.5, and centrifuging, washing and drying after reaction. The obtained immobilized lipase is firm in covalent binding, the enzyme activity is greater than or equal to 50% after the immobilized lipase is repeatedly used for 6 times, the acid-base tolerance and the storage stability are excellent, and the immobilized lipase is suitable for industrial catalysis in multiple industries.

The invention discloses an immobilized enzyme catalyst based on an epoxy modified covalent organic framework (COF) carrier and a preparation method of the immobilized enzyme catalyst, and belongs to the technical field of biological catalysis. The preparation method comprises the following steps: firstly, mixing COF-OH, epoxy chloropropane and a sodium hydroxide solution, stirring and reacting for 6-24 hours to obtain a modified material COF-EP; and dispersing COF-EP in a buffer solution, adding an enzyme solution, carrying out a constant-temperature reaction, collecting a solid product, and drying the solid product to prepare the enzyme # imgabs0 # COF-EP catalyst. By adjusting functional groups of COF, the method provides covalent binding sites for enzyme, and compared with physical adsorption, enzyme conformation change is more effectively induced, active sites are more effectively exposed, and therefore the catalytic performance is improved. The obtained catalyst has high enzyme activity, large enzyme loading capacity and excellent operation stability. The preparation method is low in cost, mild in condition and simple and convenient to operate, can be popularized to other immobilized enzyme systems, and expands the application prospect of the COF material in the field of biological catalysis.

A novel active agent-eluting hemostatic agent and methods of use and manufacture thereof are presented. A polymer, such as gelatin, is used as the base for a hemostatic agent. The gelatin is crosslinked with a chemical crosslinker, such as a carbodiimide, in the presence of an active agent. The active agent may be an anesthetic or antimicrobial, such as an antibiotic. The novel process allows for the active agent to be both covalently bound to the gelatin as well as be trapped within cages in the gelatin that are formed from the crosslinking. This dual measure allows for controlled and sustained release of the active agent from the hemostatic agent to reduce surgical site infections.

A method is provided for treating a subject with cancer using a recombinant polypeptide comprising a DRα1 domain containing a glutamine residue at the position corresponding to amino acid 45 of SEQ ID NO: 1 or SEQ ID NO: 2, or an antigenic peptide covalently bound to a portion thereof. In some cases, the subject has a tumor that is resistant to immune checkpoint blockade treatment and / or does not express a BRAF mutation. The present invention provides, for example, a method for treating a subject with cancer, comprising administering to the subject a therapeutically effective amount of a recombinant polypeptide comprising a DRα1 domain containing a glutamine residue at the position corresponding to amino acid 50 of SEQ ID NO: 1 or SEQ ID NO: 2, or an antigenic peptide covalently bound to a portion thereof; or a nucleic acid encoding the recombinant polypeptide.