46 results about "Chemical ligation" patented technology

The invention discloses warm-keeping polyimide aerogel and a preparation method thereof, and belongs to the technical field of high polymer materials. The preparation method comprises the following steps: 1, synthesizing a polyamide acid solution; 2, adding amino-containing organic silicon into the polyamide acid solution, mixing, and defoaming to form a spinning solution; step 3, preparing a nanofiber membrane by electrostatic spinning of the spinning solution; 4, crushing the nanofiber membrane, dispersing the crushed nanofiber membrane in a solvent, standing for 24-48 hours, and freeze-drying to obtain aerogel; and step 5, carrying out stepped heating thermal imidization treatment to obtain the polyimide aerogel. Amino-containing organic silicon is used as a cross-linking agent of polyamide acid, chemical connection is added for a three-dimensional network structure of the gel, and the structural stability of the aerogel is improved. In the thermal imidization process, organic silicon generates a silicon oxide and Si-O-Si network through staged pyrolysis, the silicon oxide exists in fiber gaps and forms an organic-inorganic hybrid interface with PI fibers, and the structural stability is further improved.

The invention belongs to the technical field of medical chemistry, and particularly relates to a targeted protein degradation compound containing an SYVN1 binding compound and application of the targeted protein degradation compound. According to the invention, a series of compounds interacting with SYVN1 are found, and the compounds can be used as'warheads' to participate in ERAD and effectively degrade transmembrane protein targets. Based on the SYVN1 binding compound, a new TPD technology for hijacking ERAD is established, and a brand new platform is provided for processing TMSPs and other proteins which are difficult to target by the current TPD technology. A SYVN1 interaction compound is further connected with a known ligand interacting with a protein target through a chemical linker, a series of ERADEC molecules are generated, the molecules can significantly degrade target protein, and a new possibility is provided for targeted degradation of drugs.

The invention belongs to the technical field of biological medicine, and discloses an aquatic animal antigen system and application thereof. The preparation method comprises the following steps: carrying out carboxylation treatment on bacterial cellulose to prepare carboxylated bacterial nano-cellulose, and then carrying out grafting reaction on the carboxylated bacterial nano-cellulose and an aldehyde group polymer to prepare surface modified nano-cellulose (namely poly (N-isopropylacrylamide) grafted carboxylated bacterial nano-cellulose). The surface-modified nanocellulose is used as a carrier and is chemically connected with a virus antigen protein (namely recombinant G protein) to prepare an antigen system (namely BNC-G) carrying the virus antigen protein. According to the antigen system, virus antigen protein can be delivered into aquatic animal bodies through soaking immunization, the effect of preventing and controlling aquatic animal virus diseases is achieved, and the antigen system is suitable for production of aquatic animal SPF seedlings and preparation of aquatic animal immune protection preparations.

The present invention belongs to the field of medicinal chemistry technology, specifically relating to GluA2 AMPAR endocytosis-blocking transmembrane cyclic peptides and their applications. The present invention is based on the nine active amino acid sequence (GluA2-3Y) at the end of the AMPA receptor GluA2 subunit, undergoing structural modification and engineering. A hydrophobic group is attached to the N-terminus of the peptide, and amino acids at different positions in the peptide sequence are replaced with two cysteines according to a specific pattern. The sulfhydryl groups on the cysteines are then linked using a chemical linker to partially cyclicize the peptide sequence, thereby stabilizing the peptide sequence conformation, enhancing the transmembrane ability of the modified peptide, and improving the stability of the peptide sequence.

The application discloses a bifunctional compound and use thereof, the bifunctional compound is a bifunctional compound with K-L-S structure, wherein: K is a targeting group of cyclin 7CDK7;S is a covalent group targeting cysteine or lysine on CDK7 protein;L is a divalent linking group chemically connecting the targeting group K and the covalent group S;The bifunctional compound or does not contain divalent linking group L, and the targeting group K is directly connected with the covalent group S.The bifunctional compound or its pharmaceutically acceptable salt, ester, hydrate, solvate or stereoisomer and the pharmaceutical composition containing the same show pharmacological activity related to degradation, inhibition of target protein CDK7, and can be used for preventing and treating CDK7 related diseases or disorders.

The invention discloses a synthesis method of tilpotide, and belongs to the technical field of pharmacy. According to the method, 2-Cl CTC resin is adopted as initial resin, a solid-phase polypeptide synthesis method is adopted to obtain a polypeptide fragment 1 (1-10 amino acids), then a liquid-phase reaction is performed to prepare salicylaldehyde ester of the full-protection polypeptide fragment 1, and the salicylaldehyde ester of the fragment 1 is obtained after acidolysis; rinkAmide AM resin is used as initial resin, a polypeptide solid-phase synthesis method is used for preparing a polypeptide fragment 2 (the 11th amino acid to the 39th amino acid), then salicylaldehyde ester of a polypeptide fragment 1 and the fragment 2 are subjected to STL chemical connection, then acidolysis is performed to obtain a crude product of the tilpotide, a finished product of the tilpotide is obtained after purification, the purity reaches 99.4% or above, and the yield reaches 47%. According to the method, a two-stage method is adopted, and an STL chemical connection method is used for chemical connection, so that the method has the characteristics of low cost, high yield, high crude peptide purity and the like, and is more suitable for industrial production compared with a current main four-stage process.

Provided herein are compositions of conjugates of a guide RNA(s)-CRISPR Cas protein (RNP) complex. The conjugate comprises a guide RNA(s)-CRISPR Cas protein (RNP) complex and one or more molecules selected from PEG, non-PEG polymers, ligands for cellular receptors, lipids, oligonucleotides, polysaccharides and peptides and chemically linked to the Cas protein and / or guide RNA(s). The conjugates are delivered to targeted cells as RNP complexes, or formed in targeted cells from guide RNA conjugates and a mRNA or a viral vector encoding a Cas protein, or formed in targeted cells from a crRNA conjugates and a viral vector encoding both a Cas protein and a tracrRNA. Also provided are preparation methods and uses of these conjugates.

The present invention includes a method and kit for cDNA synthesis of a 3′UTR / poly(A) tail junction of cellular RNA comprising: obtaining RNA comprising a 3′UTR / poly(A) junction and a poly(a) tail; combining the RNA with three terminating nucleotides of modified-deoxyGTP, modified-deoxyCTP and modified-deoxyATP, dNTPs, and adaptor sequence-oligo-dT; performing reverse transcription of the RNA with a reverse transcriptase primed with the adaptor sequence-oligo-dT to form terminated cDNA fragments that are stochastically terminated upstream of the 3′UTR / poly(A) junction, but not within the poly(A) tail; isolating the terminated cDNA fragments; chemically ligating a functionalized 5′ adaptor to the terminated cDNA; and amplifying the chemically-ligated cDNA into an amplification product, wherein the cDNA is enriched for sequences at the 3′UTR / poly(A) tail junction without fragmentation or enzymatic ligation.

The invention relates to a nano-silver tetrahedron lysozyme compound as well as a preparation method and application thereof. The compound is a nano particle formed by chemical connection of silver tetrahedron (Ag-t) nano particles and sulfydryl (-SH) modified lysozyme in an aqueous medium through silver-sulfydryl interaction. According to the compound, the antibacterial performance of the lysozyme can be remarkably improved through the silver tetrahedron, the antibacterial spectrum of the lysozyme is expanded, and the compound also has a good antibacterial effect on drug-resistant bacteria and can be applied to skin wounds infected by bacteria to promote wound healing.

The present invention discloses a polypeptide drug conjugate, a drug delivery system, a drug combination system and an application for synergistically enhancing tumor immunotherapy. The structural formula of the polypeptide drug conjugate is: P-L-D, wherein P is a polypeptide, D is a drug, and L is a cleavable chemical linker. The polypeptide is a pro-apoptotic polypeptide, and the drug is an indoleamine 2,3-dioxygenase (IDO) inhibitor. The polypeptide drug conjugate is prepared into nanoparticles by simple self-assembly and can be used for multiple tumor immunotherapies in vivo and in vitro. On the one hand, it can achieve the cleavage of tumor cells by the pro-apoptotic polypeptide and induce immunogenic cell death. At the same time, the combined IDO enzyme inhibitor can reverse the IDO enzyme-mediated immune metabolic pathway at the cellular level to relieve the inhibition of the immune microenvironment, and has a synergistic and enhanced tumor immunotherapy effect, and has good application prospects in the field of drug delivery.

The present invention provides novel compounds that induce selective polo-like kinase 1 (PLK1) degradation. Specifically, the present invention provides a bifunctional compound in which a PLK1 binding moiety and an E3 ubiquitin ligase-binding moiety are linked by a chemical linker. The present invention provides the compound, a method for preparing the same, and the use thereof. The compounds may be effectively utilized for preventing or treating PLK1 related diseases.

The invention discloses a charge-assisted targeting cyclodextrin carrier molecule as well as a preparation method and application thereof, the cyclodextrin carrier molecule integrates cyclodextrin, an M2pep ligand and a pH response group through chemical connection to obtain a biologically safe carrier with a clear structure and simple components. The carrier molecule is used for loading a drug and constructing nanoparticles, and cyclodextrin is responsible for loading a fluorescent dye or a nuclear drug; the M2pep ligand provides an active targeting function for the tumor; on one hand, the pH response group adjusts the surface charge of the nano-particles to enable the nano-particles to be negatively charged and prolong the blood circulation time of the medicine, and on the other hand, the nano-particles respond to an acidic tumor microenvironment and are switched into positive charges to enhance the tumor targeting of the nano-particles. In addition, the nano-particles also have the characteristics of quickly developing tumors, retaining in the tumors for a long time and quickly removing in normal organs, so that the technical problems of low tumor drug delivery efficiency and more non-target organ accumulation in the prior art are solved.

The invention provides a compound, the general formula of which is A-L-B. In the general formula, A is a chemical group which specifically binds or activates STING (stimulating interferon gene) protein; b is a chemical group specifically combined with LC3 (microtubule-associated protein-1 light chain 3) protein; l is a chemical linker. The compound can effectively mediate the degradation of STING protein and is used for treating inflammatory diseases.

The present invention provides a composition and a method for treating a disease associated with amyloid deposits of Aβ in a patient's brain, such as Alzheimer's disease. Such a method involves administering a pharmaceutical composition comprising an immunogenic fragment of Aβ capable of inducing a beneficial immune response in the form of an antibody against Aβ. The immunogenic fragment comprises a linear or polyvalent peptide of Aβ. The pharmaceutical composition comprises an immunogenic fragment chemically linked to a carrier molecule that can be administered together with an ajuvant.

The present invention discloses an antibody degrader and its application. The antibody degrader consists of three parts: a monoclonal antibody that recognizes the target protein or its antigen-binding fragment (collectively referred to as an antibody), a degrading ligand that can induce protein-targeted degradation, and a chemical linker that connects the two. The protein-targeted degrader provided by the present invention uses an antibody as the recognition group, and a specific antibody can be selected according to the actual degradation requirements. Considering the differences in the expression levels and activities of the endogenous degradation systems in different cells, in order to meet the protein-targeted degradation requirements of different types of cells, the antibody degrader of the present invention encompasses the degrading ligands involved in currently known classical degradation strategies (including proteolysis-targeting chimeras (PROTACs), autophagosome-anchoring compounds (ATTECs), chaperone-mediated autophagy chimeras (CMAs), hydrophobic tags (HyTs), etc.). The scope of application of this strategy is wide, and it can target the degradation of cell membrane proteins and intracellular proteins.

This invention provides a polyfunctional chemical conjugation molecule that has been found to be useful as a modifier for target substrates. [Solution] A polyfunctional chemical conjugation molecule is provided, comprising a localization portion, a chemical linker portion, an activator portion, a first orientation adapter that interconnects the chemical linker portion to the activator portion at one end, and optionally a second orientation adapter that interconnects the chemical linker molecule to the localization portion at a different end. The molecule provides a use for post-translational modification of a polymer that is not a natural substrate of the activator portion. Diseases or disorders may be treated or prevented by this molecule.

The invention relates to the technical field of targeted drug-loaded nanobubbles, and discloses a targeted drug-loaded nanobubble and a preparation method and application thereof, and the targeted drug-loaded nanobubble is prepared by chemically connecting GEM and cholesterol through an amide reaction. According to the scheme, the characteristic that a cholesterol shell of the nano-bubble can be combined with NPC1L1 with ultrahigh expression of pancreatic cancer cells in a targeting manner is utilized, and a chemotherapeutic drug GEM is carried on the shell of the nano-bubble, so that the targeting GEM-loaded nano-bubble is constructed. The ultrasonic molecular imaging characteristics of the nano-bubble after penetrating through tumor blood vessels and being combined with pancreatic cancer cells in a targeted manner and the effect of the nano-bubble on relieving CD8 + T cell immunosuppression in a tumor microenvironment are researched and discussed, and the effect of ultrasonic irradiation nano-bubble burst to release GEM to accurately kill pancreatic cancer cells and improve the synergistic treatment effect of the tumor immune microenvironment is clarified; a safe and effective brand-new strategy for synergistic chemotherapy and immune combined treatment is provided for diagnosis and treatment of pancreatic cancer.

The application belongs to the field of computational theoretical chemistry, and discloses a method for rapidly predicting natural chemical connection reaction rate by using a machine learning model.The method comprises the following steps: firstly, synthesizing a series of peptide thioesters containing different thioester groups to construct a peptide thioester library; then, determining the natural chemical connection reaction rates of different peptide thioesters as sample labels; subsequently, analyzing the influence of structure on the reaction rate of the peptide thioester through quantum structure optimization to obtain the feature descriptor of each sample from the calculation simulation; finally, based on the feature descriptor and the sample label, a formula of structure-function relationship is summarized by using a computer learning algorithm, so that the influence of the structure of the peptide thioester on the natural chemical connection reaction rate can be rapidly predicted.The method greatly improves the work efficiency, the result is accurate, the reproducibility is good, and the method is convenient to popularize and apply.

The invention belongs to the technical field of medicine preparation, and particularly relates to a synthesis method of retaglutide. According to the method, salicylaldehyde ester of a fragment 1 and a fragment 2 are connected through a serine / threonine connection (Ser / Thrr ligation, STL) reaction and subjected to acidolysis, crude retaglutide is obtained, and the purity of the crude peptide can reach 85% or above; furthermore, secondary high-pressure preparation and purification are adopted to obtain a final qualified retaglutide finished product, the secondary purification purity can reach 99.23% or above, and the overall yield reaches 37.7%; according to the method, a two-stage method is adopted, and an STL chemical connection method is used for chemical connection, so that the method has the characteristics of low cost, large-scale production, high yield, high crude peptide purity and the like, and the purification cost and the production cost are greatly reduced.

The present disclosure generally relates to methods for generating highly diverse barcoded bead pools via a combinatorial split-pool strategy.

The invention belongs to the field of biomedical materials, and relates to a surface hydrophilic modification method of a cotton thread, application thereof and the cotton thread for tear detection. The surface hydrophilic modification method of the cotton thread comprises the following steps: enabling the cotton thread to react with a chemical coupling agent for a certain time, then adding a hydrophilic modifier containing end amino groups into the system, and continuously reacting for a certain time to obtain the surface hydrophilic cotton thread. The chemical coupling agent is polybasic acyl chloride. The hydrophilic modifier containing the terminal amino group is one of amino-terminated chitosan, amino-terminated glucose and amino-terminated polyethylene glycol. According to the method, the chemical linking agent and hydroxyl on the surface of the cotton thread are subjected to esterification reaction, and then amino in the hydrophilic modifier and residual active sites of the chemical linking agent are subjected to amidation reaction, so that the hydrophilic modifier is linked with the cotton thread. The modified cotton thread is good in hydrophilicity, and tears can be rapidly absorbed.

Disclosed herein, in part, are novel calicheamicin derivatives with novel chemical linkers that include cleavable moieties and conjugated to targeting antibodies.

The present invention belongs to the field of biomedical technology, and discloses an aquatic animal antigen system and its application. In the present invention, bacterial cellulose is carboxylated to obtain carboxylated bacterial nanocellulose, and then it is grafted with an aldehyde polymer to obtain surface-modified nanocellulose (i.e., poly(N-isopropylacrylamide) grafted carboxylated bacterial nanocellulose). Using the surface-modified nanocellulose as a carrier, it is chemically linked with a viral antigen protein (i.e., recombinant G protein) to prepare an antigen system carrying the viral antigen protein (i.e., BNC-G). The antigen system can deliver the viral antigen protein into the body of aquatic animals through immersion immunization, achieving the effect of preventing and controlling viral diseases of aquatic animals, and is applicable to the production of SPF fry of aquatic animals and the preparation of immunoprotective agents for aquatic animals.

The present invention belongs to the technical field of medicinal chemistry, and specifically relates to a targeted protein degradation complex containing an SYVN1 binding compound and the use thereof. The present invention identifies a series of compounds that interact with SYVN1. The compounds can be used as "warheads" to participate in ERAD and effectively degrade transmembrane protein targets. On the basis of the SYVN1 binding compound, a new TPD technology for hijacking ERAD is established, providing a brand-new platform for treating TMSPs and other proteins that are difficult to target by means of current TPD technologies. Further, the compounds that interact with SYVN1 are linked, via a chemical linker, to a known ligand that interacts with a protein target, thereby generating a series of ERADEC molecules. The molecules can significantly degrade the target protein, providing a new possibility for a targeted degradation drug.

The present disclosure relates to bifunctional chemical conjugation molecules, which find utility as modifiers of target substrates. The present disclosure includes multifunctional compounds comprising an enzyme binding moiety, a chemical linker moiety, and a target binding moiety, which may further include an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post-translational modifications to proteins that are not the natural substrate of the enzyme. Diseases or disorders may be treated or prevented with molecules of the present disclosure.

The invention provides a preparation method of a [mu]-conotoxin disulfide bond substitute, which comprises the following steps: on the basis of Fmoc solid-phase synthesis and DADA module embedding technology, coupling amino acid residues under the assistance of automatic microwaves to prepare a linear precursor peptide of [mu]-conotoxin, and carrying out in-situ oxidation and thiolysis activation on the linear precursor peptide to obtain the [mu]-conotoxin disulfide bond substitute. And carrying out folding oxidation on the obtained cyclized peptide by using natural chemical connection to assist cyclization so as to form the mu-conotoxin disulfide bond substitute. According to the method, the three-dimensional conformation and biological activity of the natural peptide are kept, meanwhile, efficient and rapid synthesis of the large-span disulfide bond substituted bridging peptide is achieved, the structural stability of the peptide product is remarkably improved, the reaction condition is mild and easy to control, the process is simple, the separation yield of the target product is stable, and the method can be used for rapidly preparing various variants and has wide application prospects. Different production and research requirements are met, and good market application prospects are achieved.

The invention provides a steroid coupling drug and application thereof in drug delivery and vaccine adjuvants, a steroid and a drug molecule are coupled through a chemical linker to form a multifunctional steroid coupling drug compound, and the compound can be independently used for drug delivery and can also be used for drug delivery. The nano-particles can be used as a component of nano-particles such as micelles or vesicles for drug delivery, and can also be used as a vaccine adjuvant for enhancing immune response of vaccines and inhibiting tumor growth, so that the defects of existing drugs and vaccine adjuvants in the aspects of stability, treatment effect and multifunctionality are overcome, and an innovative technical scheme is provided for drug delivery and development of the vaccine adjuvants; important clinical values and market prospects are realized.

This invention relates to the field of advanced petrochemical new materials technology, and discloses a luminescent composite material, its preparation method, and its application. The composite material comprises the following components: homopolymer polypropylene, polybutylene succinate, a compatibility modification system, double-modified rare-earth strontium aluminate luminescent powder, dispersant, antioxidant, weathering agent, toughening agent, nucleating agent, and silane coupling agent. This invention employs a compatibility modification system composed of maleic anhydride-grafted PP-g-PBS copolymer and double-modified nano-montmorillonite. The maleic anhydride-grafted PP-g-PBS copolymer constructs a chemical link between the polypropylene and polybutylene succinate molecular chains through a grafting reaction, reducing the interfacial tension between the two resins. The double-modified nano-montmorillonite, after ionic liquid intercalation and silane grafting treatment, exhibits increased interlayer spacing and improved surface activity, uniformly dispersed in the matrix, and acts as a physical crosslinking point, improving the compatibility of the matrix resin and preventing phase separation.

Conventional cancer treatments are often ineffective, and therefore, there remains a need to develop more targeted and potent therapies to treat HCC. Antibody-drug conjugates (ADCs), which include antibodies that target GPC3 and are conjugated to cytotoxic drugs via a chemical linker, provide targeted therapies for treating patients with HCC tumors that express GPC3. [Solution] This disclosure provides GPC3 antibody-drug conjugates (ADCs), and includes compositions and methods for using such ADCs.