208 results about "Click chemistry" patented technology

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 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 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 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.

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 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.

The invention introduces novel chemical modifications to sphingomyelin and ceramide molecules, making them readily available for targeted staining and detection techniques, such as click chemistry.

The application discloses a cell-penetrating peptide-oligonucleotide delivery system prepared based on a biological orthogonal click chemical reaction and a preparation method and application thereof. The cell-penetrating peptide with a cell membrane penetration function and the oligonucleotide with a biological function are connected through the biological orthogonal click chemical reaction, so that the biological activity of the biomolecule can be better maintained, a high fidelity is provided for a wide range of functional groups, no obvious toxic side effects are caused, and the oligonucleotide delivery is efficiently realized, thereby providing a new approach for preventing and treating osteoclast activation diseases.

The embodiment of the invention provides a polypeptide antigen as well as a preparation method and application thereof. The amino acid sequence of the polypeptide antigen is Ser-Thr-Trp-Tyr-Lys-Arg, and the amino acid sequence of the polypeptide antigen is as shown in the specification. The polypeptide antigen has high conformational stability, by arranging a diphenyl cyclooctyne group (DBCO) on a side chain of a Lys residue in the polypeptide antigen and through group modification, the activity of carrying out a click chemical reaction with an endogenous or exogenous azide of a biological system is provided, and the circulation half-life period of polypeptide in a body is remarkably prolonged; through an annular structure and group modification, the polypeptide antigen can effectively target and act on T cells, and the treatment efficiency is improved.

The invention discloses a near-zero background fluorescence sensor based on polydopamine functionalized MXene as well as a preparation method and application of the near-zero background fluorescence sensor, and belongs to the technical field of universal biosensing. The sensor comprises a polydopamine functionalized MXene material and a quantum dot-aptamer fluorescent probe which is accurately coupled by click chemistry in a ratio of 1: 1. The detection method is characterized in that a target object is utilized to induce the probe to desorb from the surface of a material, and a supernatant containing the free probe is physically separated from a material precipitate through centrifugal separation, so that background fluorescence interference is almost completely eliminated. According to the invention, ultra-sensitive detection of aflatoxin B1 is realized, and the detection limit of AFB1 in complex matrixes such as corn flour is as low as 0.27 mu g / kg. All components of the platform can be modularly and independently stored for a long time, the platform can be directly applied to detection of various micromolecular mycotoxins without optimization by replacing aptamers, and the platform has high sensitivity, high stability and high universality.

The application belongs to the technical field of polymer materials and engineering, and discloses a preparation method of a phosphate cross-linked organic porous uranium extractant. A phenylacetylene is cross-linked with 1,4-dithioerythritol through a click chemistry reaction by using a photo-induced cross-linking method. Compared with common mercaptans, 1,4-dithioerythritol contains an adsorption group. The cross-linking reaction is carried out under the condition that the ratio is 1:3 and the light irradiation time is 1h. An organic polymer PCM with a porous structure is synthesized. After the synthesized polymer is subjected to Soxhlet extraction for 48h, the polymer is modified by phosphating with phosphorus oxychloride to prepare a porous polymer containing a phosphate group. After the synthesized polymer is subjected to Soxhlet extraction for 48h and is dried, a purple black powder P-PCM is obtained. The target polymer can be synthesized only through three steps of reactions. The polymer preparation is relatively simple under the photo-induced cross-linking, which is of great significance to improving the uranium adsorption capacity. The preparation is simple, the reaction is stable, the safety is high, and the cost is low through the click chemistry reaction.

The invention provides a DNA frame confinement probe, a preparation method thereof and application of the DNA frame confinement probe in drawing micromolecular mercaptan fluctuation in endolysosome. The probe comprises a frame and a functional component, the functional component comprises a small molecule mercaptan response unit and a fluorescent unit, and the functional component is connected to the frame. The framework is of a regular tetrahedral structure and is formed by an S1-8th chain, an S2 chain, an S3 chain and an S4 chain through base complementary pairing and self-assembly. The small molecule thiol response unit is a fluorescent probe CyS2 and is coupled with the S1-8th chain through a copper-free click chemical reaction. The fluorescent unit is marked at the 3'end of the S2 chain by Alexa Fluor 488 fluorescent molecules. The DNA frame confinement probe is accurate and stable in targeting, outstanding in anti-interference capability, high in clinical applicability and high in detection specificity.

The application discloses a bonded imine three-component spherical COF-based stationary phase and a preparation method and application thereof, and the preparation method comprises the following steps: S1, synthesizing an imine three-component spherical COF containing an alkyne group bonding arm; S2, bonding monosubstituted 6-azido-6-deoxy-3,5-dimethoxy anilino carbamoylated beta-cyclodextrin to the three-component spherical COF prepared in the step S1 by means of a click chemistry method to prepare a bonded imine three-component spherical COF-based chiral stationary phase. The bonded imine three-component spherical COF-based stationary phase has the advantages of simple and convenient synthesis process, good stability of the prepared bonded imine three-component spherical COF-based stationary phase and good application prospect in HPLC separation.

The invention discloses a cell membrane in-situ drug membrane protein target screening method based on variable configuration DNA, and belongs to the technical field of biological medicine. Two pairs of functionalized nucleic acid structures are constructed, the first pair is S1S2 semi-complementary DNA double strands, the second pair is S3S4 DNA-RNA hybrid double strands, and the S1S2 structure is covalently coupled to a non-natural amino acid site-directed modified membrane protein through a click chemical reaction in a living cell to realize tagging of the membrane protein; when the candidate drug coupled in S3 interacts with the membrane protein, triggering an allosteric response system to release the tagged chain in S1; the released DNA tag is subjected to PCR amplification and sequencing, and accurate identification and analysis of a membrane protein target are realized according to a tag sequence. The invention provides a high-specificity and non-in-vitro drug membrane protein target screening technology. According to the technology, active compound discovery or accurate screening of drug membrane protein targets in a living cell in-situ environment can be realized.

The application provides a composition containing Omega 3, which comprises a conjugate formed by connecting Omega 3 and a PEDF-derived peptide. The PEDF-derived peptide is obtained by truncation on the basis of a full-length PEDF protein, and the amino acid sequence is shown as SEQ ID No. 1. The Omega 3 is EPA, and the conjugate is obtained by connecting the Omega 3 and the PEDF-derived peptide through a click chemistry method. The composition can promote eye health repair, especially the treatment and improvement of dry eye, and has a clinical application prospect.

The invention provides a transformer oil acetylene degassing-free detection method and system based on click chemistry, and relates to the technical field of gas detection analysis, a first product generated by a first click chemical reaction and a second product generated by a second click chemical reaction are used as catalysts to trigger a subsequent same cascade chemical amplification reaction, and the detection result is accurate. A single product molecule can catalytically hydrolyze a large number of acid-sensitive substrates, the conductivity of a mixed solution is obvious and can be measured and changed, accurate detection of acetylene with extremely low concentration is realized, and meanwhile, acetylene detection is calculated by utilizing a second click chemical reaction synchronously generated by an internal standard reagent and a triggering agent and independent of an acetylene concentration detection process, so that the accuracy of acetylene detection is improved. According to the method, the signal ratio is obtained by calculating the ratio of the first electric signal value to the second electric signal value instead of the single first electric signal value, interference factors are offset, online self-correction of acetylene detection is realized, and high consistency and accuracy of detection results under different times and different batches of reagents are ensured.

The invention provides a novel enriched photo-crosslinking agent, a preparation method of the novel enriched photo-crosslinking agent and application of the novel enriched photo-crosslinking agent in protein conformation and protein interaction analysis. The cross-linking agent can be subjected to a cross-linking reaction with protein at the moment of illumination, a cross-linked product can be enriched through click chemistry-biotin streptavidin, then steric hindrance of the cross-linked product is reduced by cutting azido biotin groups, and the mass spectrometric detection sensitivity and specificity of the cross-linked product are effectively improved.

The invention relates to the technical field of biological medicines, particularly discloses synthesis and application of a double-target nucleic acid molecule, and provides a strategy method for connecting two nucleic acid chains through a click chemical reaction. A connection unit of triazole is generated between the two nucleic acid chains through a click chemical reaction between a nucleic acid chain (Strand 1) of an azide group and a nucleic acid chain (Strand 2) of an alkyne group, and four connection modes are selected between 5'of the Strand 1 and 3 'of the Strand 2, between 5' of the Strand 1 and 5 'of the Strand 2, between 3' of the Strand 1 and 3 'of the Strand 2, and between 3' of the Strand 1 and 5 'of the Strand 2. Furthermore, two nucleic acid chains connected with triazole are respectively combined with complementary nucleic acid chains according to complementary base pairing, so as to prepare a double-target oligonucleotide drug.

The invention belongs to the technical field of biomedical materials, and particularly relates to oxygen-enriched hydrogel for culturing vascular organs and a preparation method thereof.The preparation method comprises the steps that hyaluronic acid carboxyl and cysteine amino are covalently bound to obtain hyaluronic acid-cysteine conjugate HA-C, methacrylic anhydride and hydroxyl of an acellular matrix are subjected to an esterification reaction, and the hydrogel is obtained; the preparation method comprises the following steps: grafting methylacryloyl onto ECM (extracellular matrix) to obtain methylacryloyl modified acellular matrix ECM-MA; hA-C and ECM-MA are mixed and dissolved in a water phase, and a photoinitiator and PVP-coated calcium peroxide are added for cross-linking to form the oxygen-enriched hydrogel. The hydrogel is constructed by utilizing the sulfhydrylated hyaluronic acid and the double-bond functionalized acellular matrix by utilizing a click chemical reaction, and meanwhile, the calcium peroxide is added, so that the material has the function of releasing oxygen; the obtained hydrogel has biocompatibility, controllability and biological activity, and provides a high-performance material basis for biomedical application.

The present application relates to a kind of antibacterial polypeptide modified protein derivative and its preparation method.The protein derivative includes protein and antibacterial polypeptide, and the protein is connected between antibacterial polypeptide by triazolyl.The present application grafts antibacterial polypeptide with antibacterial activity to protein by click chemistry reaction, obtains antibacterial polypeptide modified protein derivative.The protein derivative has good biocompatibility, not only has good bactericidal effect, but also can avoid that bacteria produce drug resistance.

The invention provides a preparation method of HER2 targeted composite nanoparticles conjugated with a blood vessel disrupting agent, which comprises the following steps: grafting water-soluble azide-terminated poly (L-glutamic acid) with methoxy polyethylene glycol (NPLG-g-mPEG) to increase the number of effective load binding sites, bonding a cytotoxic drug SN38 with NPLG-g-mPEG through Steglich esterification reaction to obtain N3-PLG-SN38, and then adding the N3-PLG-SN38 into the HER2 targeted composite nanoparticles conjugated with the blood vessel disrupting agent to obtain the HER2 targeted composite nanoparticles conjugated with the blood vessel disrupting agent. According to the present invention, the Fc-PLG-SN38 is obtained by carrying out click chemical bonding on the Fc-III-4C peptide and the N3-PLG-SN38, by using the high affinity between the Fc-III-4C peptide and the Fc of the HER2 antibody, the antibody and the Fc-NPLG-SN38 are mixed in the water environment so as to obtain the HER2-PLG-SN38, and the HER2-PLG-SN38 and the blood vessel disrupting agent CA4P are conjugated so as to enhance the penetrating power and the drug effect on tumor cells;

The embodiments of the present invention relate to devices, methods and kits for assaying a disease in a subject, by selectively capturing extracellular vesicles (EVs) by click chemistry with functionalized antibodies, selectively labeling the EVs with a plurality of DNA barcodes conjugated antibodies, optionally releasing the plurality of DNA barcodes, and assaying the plurality of DNA barcodes to determine whether the disease is present or predict the stage of the disease in the subject.

The invention relates to a bio-based silane coupling agent as well as a preparation method and application thereof, and belongs to the technical field of organic material chemistry. The bio-based silane coupling agent is prepared from the following raw material components: a cardanol derivative, a mercapto silane coupling agent and a photoinitiator, and the molar ratio of carbon-carbon double bonds in the cardanol derivative to mercapto in the mercapto silane coupling agent to the photoinitiator is 1: (0.4-1): (0.01-0.05). The novel cardanol-based silane coupling agent is successfully prepared through a photo-initiation click chemistry technology. The coupling agent can significantly improve the initial bonding strength and high-temperature and high-humidity aging resistance of the adhesive, and has the advantages of environmental protection and wide application.

The invention discloses a method for preparing high-stability anionic polyacrylamide based on thiol-ene click chemistry. The core of the method is to construct an omnibearing stable system of a polymer from three dimensions through a click chemical reaction: the structure is stable: a topological chain structure with a space charge shielding effect is formed through accurate arrangement of monomers, so that a molecular skeleton and an active group keep long-acting stability. And the conformation is stable: the rigid-flexible adjustable chain segment design forms an internal microphase separation structure, so that the polymer can maintain the stretched and stable hydration conformation in various aqueous solutions, and the performance is consistent. And the process is stable: the reaction mechanism of ion complexing and click addition realizes the gentle release of polymerization heat, so that the synthesis process has high tolerance to parameter fluctuation. According to the invention, the problem of performance degradation caused by disordered structure and sensitive process of a traditional product is systematically solved, and a reliable solution is provided for the application field with strict requirements on stability.

The invention discloses a macrophage-platelet targeting delivery system carrying genes and mitochondria as well as a preparation method and application of the macrophage-platelet targeting delivery system. The platelet loaded with the PPAR gamma gene nano-composite is covalently linked to the surface of macrophage through a click chemical reaction, and a novel cell composite carrier is constructed. According to the system, the natural chemotaxis of macrophages to an injured part is fully utilized to realize precise targeting, and PPAR gamma genes and functional mitochondria are synchronously released through platelet activation in an injured microenvironment, so that the energy metabolism and lipid homeostasis of the macrophages are cooperatively regulated and controlled, the cellular burial function of the macrophages is effectively recovered, and tissue repair and regeneration are promoted. Experimental results show that the delivery system is reliable in preparation method and high in targeting efficiency, axon regeneration, myelin sheath repair and motor function recovery can be remarkably promoted in a spinal cord injury model, and a brand-new synergistic treatment strategy is provided for tissue injury repair.