512 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 present application provides stable peptide-based Botulinum neurotoxin (BoNT) serotype A 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 BoNT serotype A capture agents using iterative on-bead in situ click chemistry.

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 invention discloses a covalent lysosome targeting chimera based on a nucleic acid aptamer and application of the covalent lysosome targeting chimera in protein degradation and immunotherapy, and belongs to the technical field of biology. The invention designs a covalent lysosome targeting chimera with click chemical reaction activity, and the simple and efficient covalent lysosome targeting chimera is used for realizing efficient protein degradation at the levels of cells and living bodies. When the tool is used for targeted degradation of immunotherapy biomarkers, immunogenic apoptosis of tumor cells can be caused, so that killing of an immune system to tumors is more efficiently activated. Meanwhile, the covalent lysosome targeting chimera overcomes the problem of immune-related side effects confronted by existing antibodies and polysaccharide peptide drugs, and can effectively avoid the potential occurrence risk of the immune-related side effects while efficiently degrading the target protein.

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 invention discloses a GSH response type cell membrane bionic nano-drug, a preparation method and application, the cell membrane bionic nano-drug comprises cell membrane vesicles serving as a carrier, the cell membrane vesicles are prepared by performing cell membrane extraction and membrane extrusion on immune cells of which the membrane surfaces overexpress azide, and the cell membrane vesicles serve as a carrier. The azide on the cell membrane vesicles and the bio-coupling compound are bonded through a click chemical reaction to form-SH groups, and the-SH groups and the small-molecule inhibitor are combined together in a disulfide bond mode through the cross-linking agent. The drug is connected with a small-molecule inhibitor through a disulfide bond, so that the drug loading rate is relatively higher, the stability is better, and drug leakage in the blood circulation process is relatively less; the small-molecule inhibitor can be completely released only in a tumor site microenvironment, so that the tumor m6A methylation level is reduced, the EMT state is reversed, the tumor drug resistance is overcome, and a better tumor treatment effect is displayed in cooperation with chemotherapy drugs for tumor treatment.

The invention relates to a preparation method of a tumor microenvironment response type nano drug delivery system, which comprises the following steps: forming MnO2 nanoclusters through biomineralization induction under an alkaline condition, modifying HSA nanoparticles, then loading Ce6 through a carbodiimide method, and finally combining with a PD-L1 antibody by adopting a copper-free click chemistry method to obtain nanoparticles HMC and anti-PD-L1. The nanoparticle can be retained in a tumor tissue in a passive targeting manner through an EPR effect, and is decomposed into Mn < 2 + >, O2 and a small molecule drug through a high H2O2 and low pH microenvironment of the tumor tissue, so that the tumor permeability is greatly enhanced, the tumor immunogenicity is enhanced by combining sonodynamic therapy, the release of a tumor specific antigen and the aging of antigen presenting cells are promoted, and the tumor treatment effect is enhanced. The infiltration of tumor T cells is increased, and cold tumors are changed into hot tumors; the nanoparticles can generate O2 in situ at the same time, and the immunosuppressive ability and drug resistance caused by tumor hypoxia are overcome.

The invention relates to the field of nucleic acid fluorescence detection, in particular to a reagent and a method for detecting single-gene RNA G4 through fluorescence imaging and application of the reagent and the method. According to the invention, an RNA G4 structure targeting module and a gene sequence targeting module are adopted and are simultaneously combined to a target gene sequence and an rG4 structure in a dual-module targeting form to trigger a click chemical reaction close to triggering in a space so as to generate a nucleic acid chain of a specific sequence restored by the click chemical reaction; then, the nucleic acid sequence is used as an initiation chain, through HCR reaction, hairpins H1 and H2 are initiated to be subjected to cascade reaction, a long repeated double-chain DNA product is obtained, and fluorescence signal amplification detection can be achieved. The method has a wide application prospect.

The invention relates to the technical field of biological medicine, in particular to a nano-drug with a dual targeting effect and a preparation method and application thereof, and the nano-drug comprises exosome and ferritin; the surface of the exosome is modified with an azide group, the surface of the ferritin is modified with a cyclopentyl group, and the exosome and the ferritin are connected through a click chemical reaction between the azide group and the cyclopentyl group. According to the nano-drug, the drug carrying efficiency is improved through the exosome and the ferritin, meanwhile, the nano-drug can effectively penetrate through a cerebral blood barrier and is taken by glioma cells, and the killing effect of the drug on tumor cells is enhanced.

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.

Provided herein are methods of sequencing comprising click chemistry bioconjugation. In some embodiments, target polynucleotide sequences on the same or different molecules are contacted with and hybridize to probes comprising click functional groups. Probes (e.g., reading probes) hybridizing to adaptor sequences adjacent to different sequences of interest (e.g., barcodes to be sequenced) can be hybridized simultaneously in large pools. In some embodiments, the provided methods achieve multiplexing without requiring separate hybridization of probes (e.g., reading probes) for each sequencing-by-ligation cycle, thereby reducing total hybridization time which is typically a most time-consuming step in in situ technologies. In some aspects, the hybridized probes (e.g., reading probes) are clicked onto detectable probes to analyze a sequence of a target polynucleotide in a sequencing-by-ligation fashion.

The invention discloses a podophyllotoxin triazole ether derivative as well as a preparation method and application thereof, belongs to the technical field of chemical pharmacy, and particularly relates to a podophyllotoxin triazole derivative and application of the podophyllotoxin triazole ether derivative in preparation of antitumor drugs. A series of novel 1, 2, 3-triazole podophyllotoxin derivatives are designed and synthesized by combining a triazole structure with a podophyllotoxin matrix through click chemistry reaction, the dynamic characteristics of podophyllotoxin are optimized by introducing the triazole structure, and the anti-cancer effect and druggability of podophyllotoxin are improved. Molecular docking shows that the series of compounds have relatively strong binding energy to AKT1 and tubulin and can inhibit tubulin / AKT1 in a targeted manner, and in-vitro anti-tumor activity research shows that the molecules have very strong inhibitory activity to proliferation of human colon cancer cell strains, and a new strategy can be provided for structural derivatization of podophyllotoxin. # imgabs0 #

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 relates to hollow silicon dioxide microspheres and a preparation method thereof.The preparation method comprises the steps that an aqueous solution of a polymer, azide salt, an initiator and an organic solvent are mixed to obtain an azide-modified polymer, and the azide-modified polymer is added into a polar solvent to obtain a solution of the azide-modified polymer; mixing alkynyl-containing silane, the azido-modified polymer solution and a click chemistry catalyst, and then adding an acid catalyst or a base catalyst to carry out hydrolytic condensation reaction, so as to obtain a core-shell structure precursor of the silicon dioxide coated polymer; and carrying out roasting treatment or solvent extraction treatment on the core-shell structure precursor to obtain the hollow silicon dioxide microspheres. The preparation method provided by the invention is simple in process, relatively low in cost and relatively high in efficiency, can effectively control the particle size, the wall thickness and the density of the prepared hollow silicon dioxide microspheres, and has a wide application prospect.

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 invention discloses a glycosylation RNA (Ribonucleic Acid) imaging method based on RNA and sugar dimetabolism co-labeling. Metabolic markers Ac4ManNAz and 5-EU are taken as examples, azide and alkynyl are marked on cell surface sugar and RNA respectively, then DBCO-AF647 and N3-AF488 are connected with the azide and the alkynyl respectively through click chemistry, and two fluorophores mark the same glycosylated RNA to generate FRET signals. A laser confocal microscope is used for detection, and a green cell image of a fluorescence donor channel, a red cell image of a fluorescence receptor channel and a yellow cell image of an FRET channel can be observed respectively, so that accurate positioning of RNA, sugar and glycosylated RNA on the cell surface is realized. The invention constructs a convenient, sensitive and accurate cell surface glycosylation RNA fluorescence imaging technology, and is expected to become a powerful tool for analyzing biological functions of glycosylation RNA.

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 belongs to the technical field of phenolic resin synthesis, and particularly relates to low-temperature curing type rosin modified phenolic resin and a preparation method thereof.The low-temperature curing type rosin modified phenolic resin is prepared from, by weight, 100 parts of phenol, 150-220 parts of formaldehyde aqueous solution, 20-40 parts of rosin, 5-10 parts of diphenyl cyclooctyne-sulfydryl and 7-12 parts of diphenyl azide phosphate; the preparation method comprises the following steps: modifying traditional phenolic resin by using rosin, diphenyl cyclooctyne-sulfydryl and diphenyl azide phosphate; rosin molecules contain a plurality of carbon chains and flexible annular structures, the resin system is introduced, the acting force between the molecular chains can be weakened, carbon-carbon double bonds of the rosin molecules can be subjected to an alkene click reaction with sulfydryl of diphenyl cyclooctyne-sulfydryl, and the flexibility is improved; in order to realize low-temperature curing, diphenyl cyclooctyne-sulfydryl is introduced into synthesis of the phenolic resin, a basis is provided for click chemical reaction, and then the phenolic resin reacts with azide groups in diphenyl azide phosphate, so that a low-temperature curing effect is finally achieved.

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 discloses a trichina detection kit based on a CRISPR / Cas12a system and click chemistry as well as a use method and application thereof, and belongs to the technical field of immunological detection. The invention provides a trichina detection kit in order to solve the technical problems that a trichina detection method in the prior art is time-consuming and labor-consuming, low in sensitivity and easy to cause leak detection, a CRISPR / Cas12a system signal output probe and a manual click enzyme are complex in preparation process, and a nano material is not easy to store and transport. The kit comprises a CRISPR / Cas12a system, a click reaction system, a 96-well reaction plate, a magnetic bead probe, a colloidal gold probe, a scrubbing solution, a CuSO4 solution, an SA solution and a standard substance. The trichina detection kit provided by the invention has the advantages of high specificity, long-term stability, strong practicability, controllable quality, simplicity in operation, high sensitivity, easiness in storage and the like, can be applied to trichina detection, and has a good market prospect.