434 results about "Click chemistry" patented technology

The present application provides stable peptide-based Akt capture agents and methods of use as detection and diagnosis agents and in the treatment of diseases and disorders. The application further provides methods of manufacturing Akt capture agents using iterative on-bead in situ click chemistry.

The invention discloses photo-thermal controlled-release nitric oxide anti-biofilm hydrogel based on click reaction crosslinking as well as a preparation method and application of the photo-thermal controlled-release nitric oxide anti-biofilm hydrogel based on click reaction crosslinking, the hydrogel is prepared by taking azide group-containing four-arm polyethylene glycol and alkynyl modified hyaluronic acid as matrixes through click chemistry rapid crosslinking under the catalysis of copper-based nanoparticles, the antibacterial biological membrane has remarkable dual anti-biological membrane and anti-inflammatory effects, and can be applied to wound treatment of bacterial biological membrane infection; through a wound surface coating form, under near-infrared light irradiation, copper nanoparticles generate a mild photothermal effect to remove a biological membrane, and Cu < 2 + > is released to promote fibroblast proliferation; nitric oxide can be controllably released, a biological membrane is synergistically eliminated by enhancing lipid peroxidation and destroying a bacterial membrane structure, meanwhile, angiogenesis is promoted, collagen deposition is stimulated, and the wound healing process is accelerated; the invention has the functions of efficient antibiosis and tissue regeneration, and has wide clinical application prospect and development value in the field of infectious wound treatment.

The invention discloses a bionic lignin-based saline-alkali soil improvement material and a preparation method thereof, and belongs to the technical field of high polymer materials and soil improvement. According to the saline-alkali soil improving material, lignin or a derivative thereof serves as a framework, glutenin charge distribution and a dynamic disulfide bond sodium ion response function are simulated, and the sequence and the proportion of chain segments of sulfonic acid groups and quaternary ammonium salt groups are accurately regulated and controlled through step-by-step activation and alternate copolymerization in an aqueous solution polymerization reaction system; positive and negative charges form more uniform sequence distribution, so that the amphipathy of the lignin compound is realized; then, sulfydryl is introduced through click chemistry, linear regulation and control of material viscosity and water solubility are achieved through the chain transfer characteristic of multi-sulfydryl functional groups, and the requirements of different saline-alkali soil application scenes are met. The limitation that a traditional lignin product is single in function is broken through, efficient utilization of lignin is achieved, and the intelligent saline-alkali soil improvement material integrating high stability and pH and Na < + > multi-environment response is developed.

The invention discloses an RGD-click chemical crosslinking siRNA nano-carrier, a preparation method thereof and application of the nano-carrier in preparation of a medicine for treating secondary thyroidism, and belongs to the technical field of medicines.The nano-carrier is RGD-PEG-PLys (N), and the preparation method of the nano-carrier comprises the steps of synthesis of PLys (ss-DBCO), synthesis of RGD-PEG-PLys (N) and the like. According to the application, the nano-carrier is used for preparing siRNA composite nanoparticles; vascular endothelial targeting (RGD), dynamic stability (click crosslinking) and microenvironment responsiveness (disulfide bond) are organically combined for the first time to achieve mutual synergistic interaction, and the effect ceiling of an existing material is broken through; according to the siRNA composite nanoparticle, the silence effect of the PTH gene as long as 70 days can be achieved through single intravenous injection, the PTH inhibition rate is larger than 85%, the siRNA accumulation amount in parathyroid gland tissue is remarkably increased through RGD targeting (8.6 times that of a non-targeting group), the liver and kidney distribution amount is reduced by 60%, and the system toxicity is controllable.

The present invention discloses a method for synergistically preparing a superhydrophobic membrane by spray-induced nonsolvent phase inversion and click chemistry. The method uses a polymer with a polyvinylidene fluoride as the main structure as a raw material, constructs a micro-nano hierarchical structure in bulk by the spray-induced nonsolvent phase inversion method, and covalently bonds a low surface energy substance to the membrane surface with the assistance of click chemistry technology to achieve the superhydrophobicity of the membrane. The superhydrophobic membrane of the present invention can resist the wetting of liquids with different surface tensions, has good anti-wetting and anti-inorganic fouling properties as well as excellent wastewater treatment capabilities, and can be applied to fields such as membrane distillation seawater desalination, deep treatment of shale gas wastewater and clean water regeneration, etc., broadening the types and application ranges of MD membrane materials.

The invention discloses a silicon shell protected magnetic quantum dot nanoprobe, a preparation method, a kit and application. The nanoprobe comprises a nanomaterial and a specific antibody, the nanometer material is of a core-shell structure, and the outer surface of a core is sequentially coated with an interlayer and a protective shell layer outwards. The interlayer comprises a multi-layer laminated structure formed by alternately arranging a plurality of layers of positive electricity interlayers and negative electricity interlayers; the positive electric interlayer is polyethyleneimine, the negative electric interlayer is quantum dots, the quantum dots are CdSe / ZnS or carbon quantum dots, amino groups on the surface of the shell layer and a dialkynyl polyethylene ethanol solution are subjected to general coupling of specific antibodies in a click chemistry mode by taking diyne molecules as connecting arms. The magnetic nanoprobe with the core-shell structure not only has strong magnetic responsiveness and a high fluorescence signal, but also can adapt to a complex environment, after the magnetic nanoprobe is integrated with an immunochromatography test strip, to-be-detected targets including pathogenic bacteria and inflammatory markers can be rapidly captured in a whole blood sample at the same time, and the magnetic nanoprobe has huge application potential in early diagnosis of sepsis.

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.

The disclosure provides, for example, DNA molecules comprising at least one nucleotide with a macromolecule, small molecule, or reactive handle (e.g., click handle) appended to a phosphorothioate backbone. The disclosure also provides methods for making such DNA molecules, for example using click chemistry. In some embodiments, the DNA molecule comprises a sequence that encodes an effector (e.g., a therapeutic effector).

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 exosome engineered targeted drug delivery system and a preparation method and application thereof, and belongs to the field of biomedices.The exosome engineered targeted drug delivery system is prepared by mixing and reacting surface modified exosome and pH response type drug controlled release nanoparticles; the pH response type drug controlled release nanoparticles react with the surface modified exosome through a click chemical reaction; the surface of the membrane of which the surface is modified with the exosome is modified with a maleimide group and an azide group; the novel nano-drug has pH responsiveness; the click chemical reaction is thiol-ene click reaction. Bifunctional groups (MAL and N3) are directionally grafted on the surface of an exosome membrane, uniform drug particles are prepared in combination with a micro-fluidic technology, an efficient bimodal targeting drug delivery system is successfully constructed, and remarkable technical advantages are shown in the aspects of improving targeting precision, enhancing antitumor activity, controlling drug release, inhibiting tumor metastasis and the like; and a new technical approach is provided for precise treatment of adenoid cystic carcinoma.

The invention discloses a preparation method of a high-stability photoresponse covalent organic framework membrane and application of the high-stability photoresponse covalent organic framework membrane in selective separation of multiple components. 4-azido azobenzene is prepared by carrying out azido reaction on 4-aminoazobenzene in an acidic aqueous solution, and then a BPTA-TAPB-COF membrane is used as a matrix to prepare the high-stability photoresponse covalent organic framework membrane. 4-azido azobenzene is efficiently grafted to the pore wall of the BPTA-TAPB-COF membrane through a click chemical reaction, the photoresponse covalent organic framework membrane is constructed, and the covalent organic framework membrane can be used for multi-component selective separation and is suitable for multi-component systems with different sizes. The azobenzene group in the pore channel of the prepared Azo-COF membrane is subjected to reversible cis-trans isomerization under the irradiation of ultraviolet / visible light, the response speed is high, and the cycle performance is good; the Azo-COF membrane has good application in the light-operated nanofiltration process, the performance of the Azo-COF membrane is not reduced after the Azo-COF membrane is continuously recycled for 12 days, and the structure of the Azo-COF membrane is kept stable.

The invention discloses a pyridine quaternized cellulose derivative and a preparation method thereof, and belongs to the field of modified cellulose derivatives. According to the method, sodium carboxymethyl cellulose is taken as a raw material, and a target product is prepared through a three-step method of epoxy group grafting, sulfydryl-epoxy click chemical reaction and pyridine quaternization reaction in sequence. According to the method, the high efficiency of click chemistry and the modular design concept are innovatively introduced into the field of cellulose derivative modification, the problems that a traditional quaternization method is uncontrollable in substitution degree, many in side reaction and poor in molecular design flexibility are solved, and the method has the advantages of being mild in reaction condition, high in efficiency and clear in product structure.

The present application provides stable peptide-based antibody capture agents and methods of use as detection and diagnosis agents. The application further provides methods of manufacturing antibody capture agents using iterative on-bead in situ click chemistry.

The present application provides stable peptide-based Akt capture agents and the use thereof as detection, diagnosis, and treatment agents. The application further provides novel methods of developing stable peptide-based capture agents, including Akt capture agents, using iterative on-bead in situ click chemistry.

The invention discloses a near-infrared organic fluorescent dye with mechanical responsiveness, and relates to the technical field of organic fluorescent dyes, the near-infrared organic fluorescent dye with mechanical responsiveness is prepared through seven-step reaction, an intermediate M1 containing a hydroxyl active end is firstly prepared, then intermediates M2, M3 and M4 are obtained through multi-step reaction, a target dye is obtained after purification, and finally surface functionalized nano-particles are self-assembled, so that the near-infrared organic fluorescent dye with mechanical responsiveness is obtained. The preparation method has the advantages that by designing a conjugate regulation and control structure of a rigid chromophore core and a flexible bridging unit, a mechanical response group is directionally grafted to the tail end of the flexible bridging unit through a CuAAC click chemical reaction; the problems of low fluorescence quantum yield and high response threshold caused by conjugation conflict of a traditional mechanical response group and a near-infrared chromophore are solved, the mechanical response threshold is reduced to a low stress range required by biomechanical detection, collaborative optimization of mechanical responsiveness and near-infrared fluorescence performance is realized, and the method is suitable for the fields of high-sensitivity biological stress monitoring and the like.

The invention relates to an antibody drug conjugate as well as a preparation method and application thereof, the preparation method of the antibody drug conjugate comprises the following steps: S10, obtaining a wild type antibody, and carrying out hydrolysis reaction on galactose at the tail end of a sugar chain of the wild type antibody to obtain an antibody of which the tail end is four GlcNAc sugar types; s20, obtaining B4GALT1 (Y286L), mixing the UDP-GalNAz, the B4GALT1 (Y286L) and the antibody, and carrying out an enzymatic reaction so as to transfer the azido galactose to the tail end of a carbohydrate chain of the antibody, so as to obtain a carbohydrate chain modified antibody; and S30, mixing a target drug with the carbohydrate chain modified antibody, and carrying out a one-step click chemical reaction to obtain the antibody drug conjugate. The galactose hydrolase can retain four GlcNAc sites, and after the galactose hydrolase is connected with GalNAz, four target drug molecules can be combined, the DAR value of the antibody drug conjugate is increased, and the drug activity of the antibody drug conjugate is improved.

The invention relates to the technical field of biomedical materials, in particular to a hydroxyapatite-based face filling material and a preparation process thereof. The invention relates to a preparation process of a hydroxyapatite-based face filling material. The preparation process comprises the following steps: preparing strontium-doped hydroxyapatite; preparing composite hydroxyapatite; preparing hyaluronic acid coated hydroxyapatite; preparing an aloe extract and a moringa seed extract; and preparing the face filling material. The preparation method comprises the following steps: firstly, respectively preparing sulfhydrylated hyaluronic acid and acrylated hyaluronic acid, then mixing the sulfhydrylated hyaluronic acid and the acrylated hyaluronic acid with composite hydroxyapatite, cross-linking the hyaluronic acid under the condition of no cross-linking agent through click chemistry, and preparing hyaluronic acid coated hydroxyapatite through an organic phase curing balling method. The cross-linked hyaluronic acid is coated on the surface of the composite hydroxyapatite to form a core-shell structure, so that the potential toxicity risk caused by the residue of the cross-linking agent is eliminated from the source, and the coating rate of the hyaluronic acid on the hydroxyapatite can be effectively improved.

The present disclosure provides a hydrogel composition for tissue engineering and regenerative medicine, including naturally derived polymers functionalized with furan groups and nanoparticles of poly(lactic-co-glycolic acid)-poly(ethylene glycol) copolymer functionalized with maleimide groups. Covalent crosslinking via a bioorthogonal Diels-Alder click reaction forms a tunable, biocompatible, and biodegradable three-dimensional network. The hydrogel composition mimics the extracellular matrix and offers adjustable mechanical properties, controlled biodegradation, and therapeutic agent delivery for applications such as cartilage regeneration and drug delivery.

The invention belongs to the technical field of biological detection, and particularly relates to a bisulfite-free detection kit for specific site 5-methylcytosine and a detection method thereof. According to the method, a TAPbeta treatment method is adopted, 5hmC is sealed through beta-GT, 5mC oxidation is carried out through TET, and 5mC is reduced into dihydrouracil (DHU) through pyridine borane, so that the apparent difference between 5mC and C and 5hmC is converted into single nucleotide polymorphism difference. In addition, a flow microsphere technology based on PNA-assisted click chemical connection starting is established to detect DNA methylation specific sites. A PNA clip is innovatively introduced into click chemical connection, and non-specific connection is inhibited. Target sequence enrichment, signal amplification and signal acquisition are carried out through surface-functionalized magnetic nanoparticles, and the detection sensitivity is improved to fM. The invention provides a new tool for high-specificity and high-sensitivity epigenetic marker detection.

The invention relates to a preparation method of a nano waterproof fabric. According to the method, ellagic acid is introduced in the self-polymerization process of dopamine for in-situ reduction, a polydopamine bonding layer and a silver nanoparticle anchoring layer are synchronously constructed on the surface of nano silicon dioxide, and then perfluorodecyltriethoxysilane is catalyzed by silver nanoparticles for a regioselective click chemical reaction, so that the nano silicon dioxide is obtained. The multifunctional bionic core-shell particles with catalytic activity and super-hydrophobicity are prepared. The particles are compounded with a fluorosilicone copolymer containing dynamic disulfide bonds, a fluorosilicone polymer containing boric acid ester groups and a tannic acid-metal complex to form a double-dynamic cross-linking finishing agent system. After a fabric is subjected to ultraviolet / ozone pretreatment, discontinuous polydopamine nanodot arrays are formed on the surfaces of fibers through short-time dopamine polymerization to serve as catalytic sites, then interface priority crosslinking is triggered by utilizing the sites, and finally, dynamic keys are driven to cooperatively exchange through ultraviolet light fixation and heat treatment, so that the intelligent dynamic waterproof membrane is formed.

The invention discloses an acid and alkali resistant nanofiltration membrane and a preparation method thereof, and relates to the technical field of nanofiltration membranes. The nanofiltration membrane with better acid resistance and alkali resistance is prepared by combining a surfactant, click chemistry reaction and a metal organic framework; zirconium chloride is used as a metal node, 2-amino p-benzoic acid is used as an organic ligand, a Zr-MOF metal organic framework is constructed by adopting a solvothermal method, sulfydryl is introduced, pentaerythritol triacrylate and octyldithiol in a grafting solution are combined, free radical polymerization is carried out under UV illumination, and a high-crosslinking-degree network is formed; the charge repulsive effect of the sulphobetaine monomer realizes efficient screening of ions or molecules; a gradient ultraviolet polymerization process is adopted, and the ultraviolet intensity and density are dynamically adjusted, so that the surface flatness of the nanofiltration membrane and the uniformity of pore size distribution are improved; through chemical component design and process optimization, the mechanical property and chemical property stability of the nanofiltration membrane are synergistically improved.

The invention relates to the technical field of bio-based formaldehyde-free adhesives, and aims to provide a preparation method and application of a high-strength and high-toughness bio-based adhesive. Through interface molecular structure design, a boron nitride nanosheet based on sulfydryl click chemical function modification is constructed, an interface mechanical interlocking and chemical multi-network cross-linking reinforcing and toughening integrated technology is innovated, and the preparation method of the boron nitride nanosheet intercalation modified reinforcing and toughening plant protein adhesive is provided. The characteristic of poor interfacial adhesion between the adhesive and the wood surface is obviously improved, and the bio-based adhesive with good water resistance, high strength, excellent toughness and wider application range is obtained. According to the present invention, the dry shear strength of the plywood prepared by using the high-performance, high-strength and high-toughness bio-based adhesive through hot pressing can achieve 2.56 MPa, the wet shear strength can achieve 1.32 MPa, the wet debonding work can achieve 1800 mJ, excellent strength and excellent toughness can be represented, the thermal stability and the fire resistance of the adhesive can be significantly enhanced, and the wide industrial application prospect can be provided.

The invention discloses a zwitter-ion modified nucleic acid aptamer and a preparation method thereof, and belongs to the field of biological medicine. Wherein both the zwitterion and the aptamer have functional activity, the zwitterion has an anti-nonspecific binding effect, the aptamer can actively target a target molecule, and the zwitterion and the aptamer are coupled together through a click chemistry reaction. The zwitter-ion modified aptamer provided by the invention not only is flexible in construction mode, but also can resist the adsorption effect of proteins and cells on the aptamer, and improves the specific targeting ability of the aptamer to target molecules in a complex environment.

The invention discloses an aptamer chimera constructed on the basis of click chemistry and application of the aptamer chimera. The aptamer chimera comprises a first sequence and a second sequence which are coupled through the click chemistry reaction, the first sequence comprises a nucleic acid aptamer of a targeted target protein, and the second sequence comprises a signal peptide containing a lysosome sorting motif. The aptamer chimera disclosed by the invention does not depend on the expression of LTRs on a specific cell surface, and has a relatively good degradation effect and specificity on target protein.

The invention discloses a stem cell composition and application thereof in regulating sub-health. The stem cell composition comprises mesenchymal stem cells (MSCs) modified by fusion polypeptide and an anti-IL-6R single domain antibody. The amino acid sequence of the fusion polypeptide is as shown in SEQ ID NO.1, and the fusion polypeptide is modified on the surface of stem cells through click chemistry, so that the chemotactic migration ability, collagen matrix affinity and inflammation tolerance of the stem cells are remarkably improved. The anti-IL-6R single-domain antibody is obtained through phage display screening, the VHH gene of the anti-IL-6R single-domain antibody is shown as SEQ ID NO.2, and the anti-IL-6R single-domain antibody has high affinity and activity of inhibiting an IL-6 / STAT3 signal channel. Animal experiments show that the composition can significantly reduce inflammatory factor (IL-6) and cortisol levels of chronic stress model mice, improve oxidation resistance (SOD) and recover immune homeostasis, and provides an innovative treatment strategy for adjustment of sub-health status.

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 invention relates to a radionuclide labeled trimer probe 68Ga-TRAP-(FAPI) 3 targeting FAP and a preparation method thereof, Trap is used as a trivalent chelating platform, and three FAPI targeting units are covalently connected by clicking a chemical linking arm to form a trimer structure; the invention further relates to application of the 68Ga-TRAP-(FAPI) 3 probe in preparation of imaging agents or therapeutic drugs for diagnosing FAP positive diseases, experiments prove that the trimer probe is good in affinity and high in stability, and in cell experiments and animal experiments, the uptake rate of FAP positive cells is kept at a high level within 240 minutes; preclinical and preliminary clinical applications show that the tumor detection rate of the < 68 > Ga-TRAP-FAPI 3 in various cancer models is superior to that of < 18 > F-FDG, and compared with < 68 > Ga-FAPI-04, the < 68 > Ga-TRAP-FAPI 3 is clearer to display focuses (particularly tiny metastases), higher in uptake intensity and particularly outstanding in delayed imaging, and the < 68 > Ga-TRAP-FAPI 3 can be used for preparing a medicine for treating cancer. And a novel drug candidate with better performance is provided for precise diagnosis and staging of tumors and subsequent radionuclide targeted therapy.

The invention discloses a cyclic dinucleotide analogue containing a triazole structural unit as well as a preparation method and application of the cyclic dinucleotide analogue. The cyclic dinucleotide analogue containing the triazole structural unit is obtained by taking a macrocyclic ribose phosphate skeleton containing a diazido group as a substrate and expanding the macrocyclic ribose phosphate skeleton and an aromatic alkynyl compound through a click chemistry method, has relatively good biofilm formation inhibition activity, has a potential application prospect, and can be widely applied to biofilm biofilm formation inhibition. According to the invention, a cyclic dinucleotide analogue library is enriched, and biological research of cyclic dinucleotide and development of immunotherapy are promoted.

This invention belongs to the field of glycopolymer technology, and particularly relates to a tetraphenylethylene mono-arm thiomannose polymer with a side chain, its preparation method, and its application. The chemical structural formula of the tetraphenylethylene mono-arm thiomannose polymer is shown in formula (I). Wherein, n is an integer ≥2. The glycopolymer of this invention exhibits high biocompatibility and fluorescent recognition properties, and innovatively utilizes efficient and rapid RAFT polymerization and click chemistry to prepare the tetraphenylethylene mono-arm thiomannose polymer.

The invention discloses an orthogonal reaction regulated phase separation aggregate as well as a preparation method and application thereof. The nucleic acid protein combination capable of forming the phase separation aggregate comprises modified protein and modified nucleic acid, the nucleic acid comprises DNA and RNA, and the modified protein and the modified nucleic acid can be subjected to a click-release reaction, so that the protein and the nucleic acid are subjected to phase separation, and the phase separation aggregate is formed. The nucleic acid protein combination achieves controllable preparation of aggregates and long-acting retention of active ingredients. The nucleic acid protein composition comprises two separated components outside cells, and can form phase separation aggregates through click chemistry reaction inside cells, so that the anti-tumor effect of the medicine is improved, and the survival time of tumor mice is prolonged.