312 results about "Covalent modifier" patented technology

This invention discloses an AfBPP-based active molecular probe for thiostreptin, its preparation, and its application, belonging to the field of chemical biology. This invention introduces a bifunctional tag integrating a photocrosslinking group (bisacrididine) and a bioorthogonal reactive group (alkynyl group) into the structure of thiostreptin. While retaining the original biological activity of the parent compound, it endows the probe with highly efficient probe function, solving the technical problem of target loss during washing and purification of traditional non-covalent probes. After target labeling, the probe can specifically connect to reporter groups such as fluorescein or biotin through click-chemical reactions, achieving efficient enrichment of drug targets. Combined with mass spectrometry analysis, it enables global identification of potential targets in cells or complex biological samples at the omics level, such as chemical proteomics, providing a powerful molecular tool for in-depth revelation of the potential targets and pharmacological mechanisms of thiostreptin.

The application relates to the technical field of catalysts, and discloses a palladium / alumina catalyst and a preparation method and application thereof. A Schiff base phosphine cyclodextrin ligand is synthesized through two-step reactions of nucleophilic substitution and Schiff base condensation, the molecular structure of the ligand covalently bridges the hydrophobic cavity of beta-cyclodextrin and the strong coordination site of diphenylphosphine through a rigid Schiff base bond; subsequently, the phosphine group of the ligand is coordinated with a palladium salt under a specific pH, and a uniform and stable palladium-ligand colloid precursor is formed under the assistance of a directing agent and a stabilizing agent; finally, the colloid is mixed with an alumina carrier for impregnation, drying, and a palladium / alumina catalyst is obtained. Through molecular design and process innovation, the problems of low activity, poor selectivity and insufficient stability of traditional catalysts are solved. When the catalyst is used for preparing hydrogen peroxide by hydrogenating anthraquinone, the hydrogenation efficiency is significantly improved, the selectivity is extremely high, and the cycle stability is excellent, so the catalyst has important industrial application value.

The application belongs to the field of biomedical application, and more particularly relates to a cell fluorescence probe anchoring cell integrin, and a preparation method and application thereof. The cell fluorescence probe comprises a polypeptide complex, a fluorescent molecule and a cyclodextrin unit, the polypeptide complex comprises a cysteine-containing peptide, a peptide containing a bonding group and a targeting peptide which are connected in any order, the cyclodextrin unit contains a carbon-carbon double bond functional group, and is combined with the cysteine-containing peptide through a click reaction to form the polypeptide complex, the polypeptide complex is covalently connected to the fluorescent molecule through the bonding group, and the fluorescent molecule is an aggregation-induced emission compound. The double bond functional group of the modified cyclodextrin is bonded to the sulfhydryl group of the terminal cysteine of the polypeptide through a click reaction, and the sulfhydryl group of the terminal cysteine of the polypeptide is bonded to the double bond functional group of the modified cyclodextrin through a click reaction, so that the cyclodextrin is improved to protect the fluorescent molecule and prolong the fluorescent time effectiveness of the fluorescent imaging reagent.

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.

The application discloses a PROTAC compound with RORgamma t receptor targeted degradation and purposes thereof, which is a compound with a structure shown in a general formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutical composition thereof. e is a ligand capable of combining with an E3 ubiquitin ligase; the L is a linking group covalently combining at least one R e and at least one R W ; the R w is a target protein RORgamma t binding ligand; the application is based on the target point of RORgamma t and the PROTAC technology, and a series of RORgamma t-PROTACs are designed and synthesized for the first time. The mechanism is that the target protein ligand and the E3 ubiquitin ligase ligand are combined with POI and E3 ligase respectively, so as to form a ternary complex of "POI-PROTAC-E3 ligase". Then, the POI is marked with a ubiquitination label, and is degraded by a proteasome. The advantages of RORgamma t-PROTACs mainly include targeting of "undruggable proteins", small dosage, low toxicity, and difficulty in drug resistance. W -L-R e (I)

Provided here are IRE1 degrader compounds comprising a protein target moiety covalently attached by a linker to an E3 ubiquitin ligase-binding moiety. Also provided are intermediate compositions for the preparation of IRE 1 degrader compounds and methods of treating diseases and disorders such as cancer with the IRE1 degrader compounds.

The application belongs to the technical field of antitumor drugs, and particularly relates to an AuNRs@L / D-Ag2S QDs complex, a preparation method and application thereof. Sodium polystyrene sulfonate is electrostatically adsorbed on AuNRs to obtain 1-PSS-AuNRs; polyallylamine hydrochloride is electrostatically adsorbed on 1-PSS-AuNRs to obtain 2-PAH-AuNRs; polyallylamine hydrochloride is electrostatically adsorbed on 2-PAH-AuNRs to obtain a non-chiral nanomaterial; and the non-chiral nanomaterial is covalently crosslinked with L / D-Ag2S QDs to obtain the AuNRs@L / D-Ag2S QDs complex. The application combines the efficient photo-thermal conversion characteristics of AuNRs with the chiral-dependent targeting and potential fluorescence imaging ability of chiral Ag2S quantum dots by constructing a complex structure, so that a novel nanodiagnostic and therapeutic agent with efficient photo-thermal performance and chiral selectivity is obtained.

This invention belongs to the field of photocrosslinking probe technology, specifically relating to a GUSB photocrosslinking probe, its preparation method, and its application. The GUSB photocrosslinking probe has the general chemical formula C0. 13 H 18 N2O6-R, wherein R is any one of the oxalic group elements or peptide bonds. The R group covalently connects the glucuronic acid recognition core and the photosensitive unit in the GUSB photocrosslinking probe, and the R group contains no more than 4 atoms, resulting in a small size and low steric hindrance. The GUSB photocrosslinking probe provided by this invention uses glucuronic acid as the recognition core, combined with a small-volume diazacyclopropane photosensitive unit and a terminal alkyne group, to achieve µM-level in-situ covalent capture of active GUSB in complex systems such as cells or tissues. The probe of this invention significantly improves positioning accuracy, sensitivity, data availability, quantification, and enrichment, while also possessing advantages such as modular synthesis, mild conditions, and strong system compatibility, effectively addressing the technical shortcomings of existing technologies that struggle to accurately obtain GUSB activity in situ under low-dose conditions.

The application relates to a fusion protein and application thereof in the field of biotechnology. A polypeptide fragment for specifically recognizing a single-molecule phospholipid membrane and a polypeptide fragment for specifically recognizing a tissue or a cell are connected to form a fusion protein which can be specifically combined to a fat body surface in a non-covalent manner, so that precise targeting of the fat body is realized. The fat body targeting peptide segment can be widely used in the fields of precise drug delivery and vaccine preparation, so as to be used for treating diseases such as cancer, infectious diseases and metabolic diseases. Lung tissues and breast cancer cells are taken as target points, and good targeting of the fat body is realized.

This invention belongs to the field of biomedical materials technology, specifically disclosing a composite material for promoting the repair of soft tissue defects in the maxillofacial region and its preparation method. The composite material comprises the following raw materials: oxidized hyaluronic acid, carboxymethyl chitosan, dopamine-functionalized hydroxyapatite nanoparticles, strontium salt, copper salt, glycerol, and deionized water. The preparation method includes: firstly, strontium salt and copper salt are hierarchically loaded onto the surface of dopamine-functionalized hydroxyapatite nanoparticles via a dual mechanism of "lattice substitution-surface coordination," and then, together with oxidized hyaluronic acid and carboxymethyl chitosan, construct a "dynamic covalent-hydrogen bond-coordination bond" triple synergistic network through Schiff base reaction, hydrogen bonding, and coordination bonds. This invention solves the technical problems of poor wet surface adhesion, low mechanical strength, single function, and easy burst release of ions in existing repair materials, exhibiting excellent effects such as sequential antibacterial and repair-promoting properties, high adhesion strength, and long-lasting sustained release.

This invention provides a covalent organic framework hybrid matrix membrane, its in-situ growth method, and its application in ion separation. The method includes: dissolving cellulose derivatives, aldehyde monomers of covalent organic frameworks, and amine monomers of covalent organic frameworks in an organic solvent to obtain a first solution, a second solution, and a third solution; mixing acetic acid solution with the first, second, and third solutions to obtain a homogeneous casting solution; and drop-coating the homogeneous casting solution for in-situ growth. This invention constructs a CD@COF hybrid matrix membrane based on a cellulose derivative matrix and a low-loading covalent organic framework filler using an in-situ growth method. The prepared hybrid matrix membrane exhibits good interfacial compatibility between the matrix and the filler. The above-mentioned hybrid matrix membrane preparation process is simple, possesses good mechanical strength and high scalability, and demonstrates high ion flux and excellent ion selectivity for separating monovalent and divalent ions. It has broad application prospects in wastewater resource treatment, lithium extraction from salt lakes, and energy storage.

The application discloses a toughened composite polyurethane impact-resistant material based on dynamic covalent bond energy regulation, and belongs to the technical field of polyurethane materials. A double dynamic covalent network containing DA bonds and disulfide bonds is constructed by reacting polyurethane prepolymer, furfurylamine, cystine diethyl ester and bismaleimide, then nano molybdenum disulfide is modified by silane, then a metal-polyphenol / polymer composite interface layer is constructed on the surface of aramid fiber by tannic acid-iron complex and polyethyleneimine, finally, the components are mixed, impregnated and hot-pressed to obtain the composite polyurethane material. The application effectively dissipates impact energy through the reversible rupture and recombination of dynamic covalent bonds, and enhances the interfacial bonding force between components by using multiple interface modification, so that the material has excellent impact resistance, high strength, high ductility and efficient self-repairing function, solves the problems of easy damage of the interface of traditional composite materials, insufficient impact resistance and irreversible damage, and has wide application prospect in the fields of safety protection and buffer components.

This invention relates to a hyaluronic acid composite hydrogel based on the supramolecular self-assembly of natural molecules and its preparation method, belonging to the field of gel formulation technology. The invention first involves the self-assembly of specific natural molecules or their derivatives possessing hyaluronidase inhibitory and anti-inflammatory activities into stable supramolecular self-assemblies through intermolecular non-covalent interactions. Subsequently, this supramolecular self-assembly is combined with hyaluronic acid through various interactions such as physical entanglement, hydrogen bonding, van der Waals forces, or appropriate chemical cross-linking to construct a composite hydrogel with a uniform internal structure and stable performance. This invention not only achieves long-term, controllable sustained release of natural active ingredients in the gel through supramolecular loading, continuously inhibiting hyaluronidase activity and local inflammatory responses, but also avoids the residual risks associated with high dosages of traditional chemical cross-linking agents, ultimately obtaining a high-quality product that meets the appearance and performance requirements of medical hyaluronic acid gels.

The application provides a mass spectrometry detection device and method for active protein-small molecule interaction, which uses a mass spectrometry sensor to obtain tandem mass spectrometry data of non-covalent complexes of active protein incubated with small molecule compounds at different concentration points; performs non-linear curve fitting on the concentration sequence of the small molecule compounds based on the ion combination rate of the protein binding small molecules at each concentration point, to obtain an apparent dissociation constant of the active protein-small molecule interaction; determines a local conformation change parameter of the active protein induced by small molecule binding and a potential binding domain of the small molecule; and performs fusion evaluation on the binding strength and conformation influence degree of the protein-small molecule interaction based on the apparent dissociation constant, the local conformation change parameter and the potential binding domain, to output a stability grade of the protein-small molecule interaction. Based on the above scheme, non-denatured state mass spectrometry detection of protein-small molecule complexes in a liquid phase environment can be realized.

An oral pouch comprising a pouch envelope made of a chemically bonded nonwoven fabric which contains cellulose fibers and during the production of which an additional crosslinking agent that can form a covalent chemical bond, e.g. by means of ester or ether bonds, with cellulose molecules was added to the binder, and said oral pouch comprising a filling material arranged in the pouch envelope.

The application discloses a high-stability immobilized mannanase and a preparation method and application thereof, and belongs to the technical field of enzyme immobilization. The preparation method uses PAMAM modified SBA-15 / calcium alginate composite microspheres as a carrier to fix mannanase in an enzyme solution by adopting an embedding-covalent crosslinking method, so as to obtain the high-stability immobilized mannanase. The preparation method uses the PAMAM modified SBA-15 / calcium alginate composite microspheres as the carrier to fix the mannanase by adopting the embedding-covalent crosslinking synergistic method, so that the pH tolerance, the circulation stability and the hypoglycemic efficiency of the enzyme are improved, and the problems of the traditional immobilized enzyme, such as large enzyme activity loss, easy leakage and poor stability under high temperature, are solved.

This invention discloses a magnetic covalent organic framework composite material modified with nucleic acid aptamers, its preparation method, and its applications. The composite material uses magnetic iron oxide microspheres as the core, with the surface of the core coated with a shell of covalent organic framework material. Nucleic acid aptamers capable of specifically recognizing tetracycline antibiotics are stably assembled onto the shell surface through non-covalent interactions. This invention fully utilizes the large specific surface area and electron-rich framework of magnetic covalent organic framework materials as efficient carriers for nucleic acid aptamers, effectively overcoming the shortcomings of traditional adsorption materials in terms of poor selectivity and limited adsorption capacity in complex matrices, while avoiding cumbersome covalent modification processes. This composite material exhibits excellent adsorption capacity and superior selectivity for tetracycline antibiotics, and is particularly suitable for rapid and efficient magnetic solid-phase extraction of trace tetracycline antibiotics in complex animal-derived food matrices, significantly improving the detection sensitivity and accuracy of subsequent instrumental analysis.

The embodiment of the present application provides a Fe3O4@COF electrochemical sensor based on a covalent organic framework, a preparation method and application, the electrochemical sensor comprises: a base electrode which is surface-modified with a solid film; the solid film is a Fe3O4@COF composite material; the Fe3O4@COF composite material comprises: a core formed by a porous structure of Fe3O4 and a COF shell layer attached to the surface of the core; the COF shell layer is a covalent organic framework layer formed by copolymerization of aromatic aldehyde compounds and polyamino aromatic compounds. The Fe3O4@COF electrochemical sensor based on the covalent organic framework, the preparation method and the application can detect quinolone antibiotic molecules such as norfloxacin, and the detection limit can reach 1.927*10 ‑ 13 mol / L; and can be widely applied to the detection of quinolone antibiotics such as norfloxacin in milk and environmental water samples.

The application discloses a kind of high-efficiency antibacterial modified silica gel and preparation method thereof, with food-grade liquid silica gel as matrix, using polylactic acid-polylysine block copolymer as degradable biological antibacterial unit, through silane coupling agent in situ covalent graft modification under room temperature ultraviolet light, make antibacterial unit firmly bonded in silica gel molecular chain.The obtained silica gel antibacterial rate is greater than or equal to 99.9%, and there is no precipitation after multiple water boiling disinfection, the antibacterial unit is biodegradable, the process is green, low energy consumption, no harmful substance residue, high safety, suitable for infant nipple, dental cement and other entry products, solve the problems such as easy precipitation, non-degradable and environmental unfriendly of traditional antibacterial silica gel.

The present disclosure relates to the antibodies specific targeting CD142, antibody-drug conjugates, preparations and uses thereof. The antibody or antigen-binding fragment thereof binding to CD142 is covalently linked to a cytotoxic payload through a linker. The antibody or antigen-binding fragment thereof binding to CD142 and the antibody-drug conjugate exhibit cytotoxic effects on tumor cells.

This invention discloses a layer-by-layer deposition modified ultrafiltration membrane with both antifouling and antibacterial properties, its preparation method, and its applications. Through layer-by-layer assembly technology, a tannic acid (TA) anion layer and a polyhexamethylene biguanide (PHMB) cation layer are alternately deposited on the surface of an ultrafiltration membrane. Under weakly alkaline conditions, electrostatic interactions, hydrogen bonding, Schiff base reactions, and Michael addition reactions are simultaneously utilized to achieve both non-covalent and covalent bonding, constructing a stable and dense integrated antibacterial-antifouling composite coating. This coating has a contact-type antibacterial structure, which can effectively kill bacteria in water and inhibit biofilm formation at the source. Simultaneously, it significantly improves the hydrophilicity of the membrane surface, reduces pollutant adsorption and deposition, and achieves synergistic enhancement of antibacterial and antifouling properties. The preparation process of this invention is mild, simple, low-cost, and environmentally friendly. The modified membrane exhibits high flux retention, excellent separation performance, and excellent operational stability, and can be widely applied in water treatment scenarios such as municipal wastewater treatment.

Disclosed herein is a molecule, or a pharmaceutically acceptable salt thereof, that has a formula M1DO1-L-ME3, M1DO1 is a moiety that binds to IDO1, L is a linker covalently attaching M1DO1 and ME3, and ME3 is a moiety that binds to an E3 ubiquitin ligase. Disclosed herein are also the uses of the molecule, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same, in a method of treating cancer in a subject in need thereof.

The disclosure belongs to a field of environmentally friendly new materials, specifically relating to a modified covalent organic framework for simultaneous adsorption of multiple heavy metal ions, along with its preparation method and applications. The preparation steps for the material are as follows. 1,3,5-tris(4-aminophenyl)benzene and 2,5-dihydroxyterephthalaldehyde are dissolved in a mixed solvent and allowed to stand and react at room temperature to obtain a mixed solution. Scandium trifluoromethanesulfonate is added to the obtained mixed solution, and allowed to stand and react at the room temperature. After completion of the reaction, the insoluble matter is separated from the reaction solution, and the insoluble matter is washed and dried to obtain a covalent organic framework substrate. A neutral solution is used to perform an ultrasonic modification treatment on the covalent organic framework substrate prepared, and then the modified substrate is washed and dried to obtain a modified covalent organic framework.

The present invention relates among other aspects to a conjugate or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising said conjugate or its pharmaceutically acceptable salt for use in a method of preventing or treating an infection, wherein said conjugate is water-insoluble and comprises a polymeric moiety —Z to which a plurality of moieties -L2-X0D-L1-D are covalently conjugated, wherein each -D is independently an antibiotic moiety; each -L1- is independently a linker moiety to which -D is covalently and reversibly conjugated; each —X0D— is independently absent or a linkage and each -L2- is independently either a chemical bond or a spacer moiety.

The present invention provides a method for synthesis of a novel covalent organic framework material having a 12-crown-4-ether group based on chiral separation. The novel covalent organic framework material having a 12-crown-4-ether group is prepared in the present invention, and CCOF-HTOD-1 can be used as a fluorescent probe for achieving chiral separation of different chiral drugs (L-PGL, D-PGL, L-PAL, D-TPL, L-TPL and D-TPL). The CCOF-HTOD-1 prepared in the present invention not only has advantages such as a simple preparation method, suitability for large-scale production, a uniform structure for the prepared novel 12-crown-4-ether covalent organic framework material, ease of dispersion, and excellent CD optical activity, but also exhibits excellent performance in detection of various chiral drugs, including high detection efficiency, high selectivity, and recycling. As a result, common problems in chiral drugs, such as difficult separation and low detection efficiency, can be solved thereby.

The present application relates to the technical field of porphyrin-based covalent organic framework material preparation, in particular to a mild preparation method of acetaldehyde-based porphyrin covalent organic framework and application thereof, which comprises the following steps: step one: dispersing ligand 2', 5'-bis((ethyl sulfide) methyl)-[1,1':4',1''-triphenyl]-4,4''-diamine in acetonitrile solution to obtain solution A, and dissolving acetaldehyde-based porphyrin in dichloromethane to obtain solution B; step two: mixing solution A and solution B; step three: adding ferric chloride and acetic acid as catalysts to react under mild conditions to obtain acetaldehyde-based porphyrin covalent organic framework material, which has excellent gaseous iodine adsorption performance. The synthesis method provided by the present application has mild conditions, simplifies the high-temperature time-consuming shortcomings of traditional porphyrin-based covalent organic framework material synthesis, and realizes the synthesis of special ligand covalent organic framework.

a kind of sp 2 C covalent organic framework functionalized silicon-based chromatographic stationary phases, their preparation methods, and applications. Preparation steps: (1) Preparation of SiO2-NH2: Aminated activated spherical silica particles are prepared using an amino-containing silane coupling agent; (2) SiO2@sp 2 C-COF preparation: Using TMT and TFPT as raw materials, sp was obtained through a Schiff base-mediated aldehyde-alcohol condensation reaction initiated by a self-assembled monolayer auxiliary surface. 2 A C covalent organic framework is loaded onto the surface of a silica matrix via C=N bonds. 2 C-COF possesses an in-plane π-conjugated, highly ordered, and robust framework structure. Its unique hydrophilic covalent triazine groups and hydrophobic benzene rings can provide various interactions such as hydrophobicity, π-π stacking, hydrogen bonding, and hydrophilicity. This enables the stationary relative shape-restricted and geometric isomers to exhibit special selectivity and separation capabilities, overcoming the instability of common imine-bonded COFs in liquid chromatography (HPLC) and the limited selectivity of relatively shape-restricted and geometric isomers stationed in traditional bonded silica gel.