34 results about "Disulphide bonds" patented technology

The application discloses application of a PDIL2;3 gene in regulation of rice grain type and chalkiness. The application provides, for the first time, important regulation of a protein disulfide isomerase coding gene PDIL2;3 on the grain type and chalkiness of rice, and a spike becomes larger, a grain becomes longer, a grain width becomes wider, the thousand-grain weight increases and the chalkiness increases by knocking out or destroying the normal expression level of the PDIL2;3 gene, so as to obtain an ideal rice grain type, improve the rice quality, provide a new approach for high-yield and high-quality breeding of rice, and have a wide application prospect.

Compositions are disclosed that include at least one protein disulfide isomerase or a biologically active fragment or variant thereof. Methods of producing and using the compositions are also disclosed. In particular (but not by way of limitation), methods are provided for reducing blood glucose, treating hyperglycemia, treating or reducing the occurrence of type 1 diabetes, treating or reducing the occurrence of type 2 diabetes, and / or treating or reducing the occurrence of type 3 diabetes (i.e., Alzheimer's Disease) by administering the composition that includes the at least one protein disulfide isomerase. The protein disulfide isomerase may be administered alone or may be administered simultaneously or sequentially with one or more additional active agents.

The invention relates to the technical field of biomedical materials, in particular to a high-molecular polymer as well as a preparation method and application thereof in delivery of nucleic acid. The high-molecular polymer has a structure as shown in a formula I. The polymer has good in-vivo and in-vitro nucleic acid drug delivery performance due to good GSH responsiveness, has excellent biodegradability and small toxic and side effects, can be used as a nucleic acid drug delivery carrier, and can be rapidly degraded and release nucleic acid by taking a disulfide bond as a main chain to respond to glutathione (GSH) widely existing in cells; meanwhile, degraded small molecules can be quickly discharged out of a body and have no obvious toxicity to cells and mice. After caudal intravenous injection, the high-molecular polymer can realize spleen-targeted and lung-targeted efficient delivery of nucleic acid drugs, so that the high-molecular polymer is used as a nucleic acid drug delivery carrier to be combined with the nucleic acid drugs, and has great significance in preparation of drugs for treating genetic diseases, tumors, virus infection and other diseases.

An anti-immunoglobulin specific antibody (or fragment thereof), characterised that the antibody or fragment thereof comprises one or more non-disulphide cross-links between at least one heavy chain or fragment thereof and at least one light chain or fragment thereof of the antibody or fragment thereof. A method purifying an anti-immunoglobulin specific antibody (or fragment thereof), characterised that the antibody or fragment thereof comprises one or more non-disulphide cross-links between at least one heavy chain or fragment thereof and at least one light chain or fragment thereof of the antibody or fragment thereof. A method of quantifying an amount of a subject analyte, or a fragment of an analyte in a sample from the subject comprising: (i) adding to the sample a predetermined amount of one or more control analytes or fragments thereof, which are distinguishable from the equivalent subject analyte or fragment; (ii) measuring the relative amount of the subject analyte or fragment and the amount of the control analyte or fragment in the sample; and (iii) comparing the relative amount of subject analyte or fragment to the relative amount of control analyte or fragment, to quantify the amount of analyte or fragment in the original subject sample.

The present invention provides vaccine compositions, methods and uses thereof, the vaccine compositions are immunogenic compositions of secreted fusion proteins, wherein the secreted fusion proteins comprise a rabies or soluble influenza virus antigen linked by in-frame fusion to a collagen C-terminal portion capable of self-trimerization to form a disulfide-linked trimeric fusion protein. The present invention also provides uses of the immunogenic compositions for generating an immune response against rabies or influenza infection and for use in vaccine compositions. The present invention also provides methods of producing recombinant peptides and proteins, methods of prevention, treatment and / or diagnosis and related kits.

A method comprising the steps of: (a) assessing an expression level of at least one protein, selected from Table 1, 2 or 3 in a sample from a subject, where in the at least one protein may be selected from the list comprising: Beta-Ala-His dipeptidase, Apolipoprotein L1, Methanethiol oxidase, Vitamin K-dependent protein S, von Willebrand factor, Plasminogen, Selenoprotein P, Protein disulfide-isomerase A6 and Inter-alpha-trypsin inhibitor heavy chain H3, and (b) using the expression level to determine whether the subject has endometriosis.

This invention discloses a novel class of peptides for targeted cancer therapy and their corresponding drug or fluorescent dye conjugates, belonging to the field of biomedical technology. These peptides are designed based on the optimized structure of natural LHRH-III, enabling them to specifically bind to and efficiently internalize into tumor cells overexpressing luteinizing hormone-releasing hormone receptor (LHRH-R). After fluorescent conjugation, their targeting ability against 4T1 cells is comparable to that of the classic peptide [D-Lys]. 6 The [-LHRH-I] peptide exhibits comparable to or superior performance and significantly improves cellular internalization efficiency. In vivo distribution studies have shown that its liver accumulation is significantly reduced compared to the control group, effectively lowering the risk of hepatotoxicity. Furthermore, by conjugating the targeting peptide with antitumor drugs (such as camptothecin or doxorubicin) via disulfide linkers, the resulting peptide-drug conjugates (PDCs) demonstrate excellent responsive drug release characteristics and good in vitro and in vivo antitumor activity. The peptides and conjugates provided by this invention have potential application value in cancer targeted therapy and diagnosis with high specificity and low toxicity.

The present invention generally pertains to methods of preventing disulfide scrambling in non-reducing liquid chromatography-mass spectrometry analysis of a protein of interest. In particular, the present invention pertains to the addition of maleimide to a non-reducing liquid chromatography-mass spectrometry analysis of a protein to prevent disulfide scrambling.

The invention relates to a hair care composition comprising malic acid, arginine and shikimic acid, and to the use of said components in the manufacture of a hair care composition.

The invention belongs to the technical field of biological medicines, and discloses a cyclized antibacterial peptide CycP-1 targeting multiple drug-resistant klebsiella pneumoniae, and a composition and application thereof. The amino acid sequence of the antibacterial peptide is shown as SEQ ID NO.1, cysteine residues at the first site and the 24th site in a molecule of the antibacterial peptide form a disulfide bond, and the antibacterial peptide is in cyclization conformation and shows good in-vitro protease stability. Experiments show that the antibacterial peptide has a remarkable inhibiting effect on multi-drug-resistant and pan-drug-resistant klebsiella pneumoniae, and when the antibacterial peptide is combined with antibiotics, the antibacterial effect can be enhanced, drug resistance can be reversed or reduced, and generation of drug resistance can be delayed. A mouse pneumonia model in-vivo experiment further proves that after oral administration of the antibacterial peptide, the lung tissue bacterial load of a pan-drug resistant klebsiella pneumonia infected mouse can be remarkably reduced, lung pathological injury is relieved, the survival rate of the infected mouse is remarkably increased, and the effect is better when the antibacterial peptide is combined with polymyxin B.

The present invention relates to the generation of a library of cysteine-enriched macrocyclic peptide sequences expressed on the surface of yeast cells, methods for their preparation and a population of yeast cells genetically modified to express a plurality of disulfide tethered macrocyclic peptide ligands having different structures and amino acid sequences on the surface of yeast cells.

The invention discloses a double-target-point cyclic peptide and a synthesis method and medical application thereof.The amino acid sequence of the double-target-point cyclic peptide is Cys-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Alaa-Cys-Lys-Pro-Ser-Trp-Arg-Alaa-Asp, Cys1 and Cys10 form a cyclic peptide structure through disulfide bond cyclization, the relative positions of the N terminal and the C terminal are stabilized, the enzyme resistance and the structural stability are improved, and the double-target-point cyclic peptide has the advantages that the double-target-point cyclic peptide is obtained; further, protease degradation is resisted, the half-life period is prolonged, and efficient analgesia is realized by synergistically activating a mu opioid receptor and inhibiting a voltage-gated sodium ion channel 1.8. The double-target cyclopeptide designed by the invention has the beneficial characteristics of simple structure, convenience in artificial synthesis, low production cost and the like, and has huge medical industrial applicability.

Provided are proteins and peptides suitable for binding lanthanide ions and / or actinide ions. Proteins of the present disclosure may contain or be one of the following sequences: DDKAACAX1GIAAVKAX2VEKLAPEAVPQKLKRALKIAEREQGEGX 3FX4X5CLX6ALX7DAKRALPKX8X9 (SEQ ID NO:1) or MMRTRTSLAVPRGFRGSALLADDKAACAX1GIAAVKAX2VEKLA-PEAVPQKLKRALKIAEREQGEGX3FX4X5CLX6ALX7DAKRALPKX8X9 (SEQ ID NO:52), where X1 is D or S; X2 is R or K; X3 is E, Q, or M; X4 is D, N, Q, or K; X5 E, N, Q, D, A, or T; X6 is E, A, or Q; X7 is D or E; X8 is Y, W, or absent; and X9 is G or absent, or a protein having at least 70% identity to SEQ ID NO:1 or 52. Proteins or peptides of the present disclosure may contain a metal-binding motif or be REX1X2EX3EX4DEC (SEQ ID NO:53), where X1 is any amino acid; X2 is any amino acid, (e.g., G, A, K, R); X3 is any amino acid, (e.g., G, A, or K); and X4 is F or Y; and the C forms a disulfide bond with another cysteine residue elsewhere in the peptide. Also provided are methods of using any one of the proteins or peptides, methods of making any one of the proteins or peptides, and kits.

Provided herein are methods and host cells for producing a polypeptide containing two chains, such as an antibody, half-antibody, antibody fragment, or one-armed antibody. The methods and host cells allow for two-chain polypeptide production using expression of polynucleotides encoding the polypeptide chains from extra-chromosomal polynucleotide(s), and expression of one or more chaperone protein(s) (e.g., peptidyl-prolyl isomerases and / or protein disulfide oxidoreductases) from the host cell chromosome using non-native combination(s) of promoters and translational units encoding a chaperone protein.

This invention discloses a method for constructing disulfide mimetic compounds for late cyclization of peptides. The disclosed method provides late cyclization via thioacetalization of peptides containing two cysteine ​​residues to form a thioacetal group. These bonds are stable under acidic, basic, and reducing conditions. A wide range of cyclic ketones, and even acetone, can be used as crosslinking agents in this reaction. Since trifluoroacetic acid (TFA) can function as both a catalyst and the sole solvent, most peptide sequences can be cyclized by the disclosed method. The disclosed method offers many advantages and merits, including the use of TFA as a robust catalyst and the sole required solvent, the readily available availability of acetone and a variety of cyclic ketones as reactants, good chemoselectivity and tolerance of natural peptides to this reaction, and the fact that the resulting crosslinks are structural mimetic compounds of disulfides.

The application discloses a disulfide-containing lipid molecule for mRNA delivery and a preparation method and application thereof, and a synthesis method of the lipid molecule is as follows: 2,2-dithiodiethanol diacrylate is used as a raw material, and is further reacted with selected hydrophilic amines to generate an intermediate, and the intermediate is further reacted with hydrophobic amines to obtain a final lipid molecule for delivering mRNA, wherein the hydrophilic amine raw material is one of 4A1, 4A2 and 4A3; the hydrophobic amine raw material is one of C18, 2C8 and 2C10; the prepared lipid molecule contains a head group generating a cation by ionization, and nucleic acids carry a negative charge, so that the two can be efficiently combined, thereby significantly improving the loading rate of nucleic acids. And the carbon chain length and the number of branches of the hydrophobic alkane chain have a crucial influence on the stability of the formed nanoparticles, so that the lipid molecule has a good prospect in the application of delivering mRNA molecules.

To provide a method for treating inflammatory bowel disease (IBD).SOLUTION: The present invention relates to methods of treating inflammatory bowel diseases, including with engineered peptides (e.g. peptide monomers and dimers comprising disulfide or thioether intramolecular bonds) that bind α4β7 integrin. In one aspect, the disclosure provides a method of treating an inflammatory bowel disease (IBD) in a subject in need thereof, comprising administering to the subject an α4β7 integrin antagonist, wherein the antagonist is administered to the patient orally at a dose of about 100 mg to about 500 mg, once or twice daily, wherein the antagonist is a peptide dimer compound comprising two peptides, or a pharmaceutically acceptable salt thereof.SELECTED DRAWING: Figure 22

Compounds according to formula (I) are described wherein R1 is an amino acid or a modified amino acid linked to the compound through a peptide bond, R2 is selected from CN, SO2CH3, NO2, CO2R3, CONHR3, NH2, NMe2 and CF3, and R3 is selected from H or lower alkyl, X is O or S, and Y is C—H or N, or a pharmaceutically acceptable salt thereof. The compounds can be used as protein disulfide isomerase inhibitors. The compounds can also be used in a method of treating or cancer in a subject.

This invention discloses an oligomeric wheat peptide and its preparation method, belonging to the field of plant peptide technology. The method uses wheat bran as raw material, which undergoes extrusion puffing and ultrafine grinding pretreatment, followed by alkaline extraction combined with amylase hydrolysis to obtain a wheat bran protein extract. Subsequently, it undergoes low-temperature controlled denaturation pretreatment, followed by freeze-thaw cycles to partially unfold the protein. Cysteine ​​is added as a conformation-locking agent to form reversible mixed disulfide bonds with exposed free thiol groups to stabilize the metastable conformation. Then, site-specific enzymatic hydrolysis is performed in an ultrasound-assisted enzyme membrane reactor, with ultrafiltration separating the oligopeptides in real time. Finally, electrodialysis desalination, nanofiltration concentration, and spray drying yield high-purity wheat bran oligomeric wheat peptides with gastric mucosal protective activity. This invention achieves high-value utilization of wheat bran components, with a green and efficient process, and produces peptides with high uniformity and strong activity, significantly improving the quality and market competitiveness of wheat peptide products.

Described herein is a dual-functional tetrazine–allyl reagent that enables site-selective disulfide modification in peptides and proteins, serving both as a Michael acceptor for bis-thiols and as a reactive handle for Inverse Electron-Demand Diels–Alder (IEDDA) click chemistry to introduce functional payloads.

To provide a novel compound that is suitable for a variety of applications including inhibition of PDI activity, and to provide, using the novel compound, a novel PDI activity inhibitor, a novel apoptosis inducer, a novel anticancer agent, a novel agent for treating infectious diseases, or a novel blood coagulation inhibitor.SOLUTION: A compound represented by General Formula (1) below, wherein X1 is a hydroxy group, an oxygen atom, an ethylamino group, or a diethylamino group; Y1 to Y4 are independently a hydrogen atom, a methyl group, a fluorine atom, a chlorine atom, or a bromine atom; Z1 to Z3 are independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group, or a nitro group, with at least one of Z1 to Z3 being a nitro group; and Z4 to Z7 are independently a hydrogen atom or an alkyl group.SELECTED DRAWING: None

The present disclosure relates to disulphide-linked oligomerization domains for oligomerization of polypeptide fragments. The disulphide-linked 5 oligomerization domain, according to embodiments herein, facilitate correct folding and assembly of proteins into their functional oligomeric forms, and enhances the stability and immunogenicity of oligomeric proteins. Also disclosed are polypeptides having the disulphide-linked oligomerization domains linked to antigenic peptides, and a pharmaceutically acceptable carrier. 10 The present disclosure further relates to compositions, nucleotides, recombinant host cells, and methods for producing the polypeptides as disclosed herein.

A photocurable resin composition comprising a crosslinker (104), the crosslinker (104) comprising plural cyclic disulphide groups and wherein the concentration of disulphide bonds in the resin composition is at least 10 wt. %.

The invention provides inhalable microgel with enzyme responsiveness and a preparation method of the inhalable microgel, and belongs to the technical field of inhalation type preparations. Microgel constructed by a cross-linking agent with MMP2 enzyme responsiveness serves as a carrier, nintedanib and trastuzumab are jointly entrapped, enzyme-triggered targeted release of the medicine at the pulmonary fibrosis part is achieved through inhalation administration, and the curative effect is synergistically enhanced; the preparation method of the microgel comprises the following steps: preparing nintedanib lipidosome, and reducing disulfide bonds of trastuzumab; the preparation method comprises the following steps: preparing a nintedanib lipidosome and trastuzumab through a sulfydryl-maleimide reaction to obtain a solution containing free sulfydryl, connecting the nintedanib lipidosome and trastuzumab through the sulfydryl-maleimide reaction, mixing the nintedanib lipidosome solution connected with trastuzumab with a cross-linking agent prepared from CPVGLIDC and 4-arm polyethylene glycol maleimide according to a molar ratio of 1: 1, and preparing microgel through a water-in-oil emulsification method; and finally, carrying out gradient centrifugal screening to obtain microgels with three particle sizes. Nintedanib and trastuzumab synergistically enhance the anti-pulmonary fibrosis effect, and the effect is better than that of single-drug treatment.

The invention relates to an application of camelliin B in inhibiting the activity of protein disulfide bond isomerase. The invention discloses a novel application of camellia glycoside B. On the basis of finding that a natural flavonoid compound camellia glycoside B has the activity of inhibiting protein disulfide isomerase (PDI), the application of the camellia glycoside B as an active component in the field of PDI inhibition is proposed for the first time. Experiments prove that low-dose camellia glycoside B can efficiently inhibit PDI activity, and the median inhibitory concentration (IC50) of the camellia glycoside B is 7.3 [mu] M. The discovery provides an important candidate compound for developing a novel PDI inhibitor, has key significance in research and development of drugs for PDI-related diseases such as thrombotic disease prevention and treatment, tumor intervention and the like, and has broad application prospects. Meanwhile, a new direction is opened up for application of natural products in enzyme activity regulation and control.

The invention relates to a new group of aromatic sulphonamides derivatives of formula (I) and their synthesis and use for modulation of the activity of protein disulfide isomerase (PDI). More particularly, the invention provides small molecule inhibitors of PDI A3 that display antiplatelet, antithrombotic and anticancer activities.

This invention discloses the preparation and application of a recombinant cholesterol esterase immobilized enzyme preparation. This invention will... Ophiostoma piceae Cholesterol esterase mutant gene ope-D136P Linked to pPICZαA plasmid, via signal peptide replacement and rDNA Gene insertion yielded the pEESB-3 plasmid; the protein disulfide isomerase gene was inserted. pdi The pPIC9K plasmid was ligated to obtain the pEESB-4 plasmid. This plasmid was electroporated into Pichia pastoris GS115, and after resistance selection and methanol-induced expression selection, recombinant Pichia pastoris engineered strains were obtained. Recombinant cholesterol esterase was obtained from this strain after methanol-induced expression. An aminated immobilization vector was prepared using APTES and TEOS as silane precursors. After grafting with 2,4-dihydroxyacetophenone and nickel ion chelation, the recombinant cholesterol esterase was immobilized to obtain an immobilized enzyme preparation. This immobilized enzyme preparation can catalyze the synthesis of stigmasterol ferulic acid ester from stigmasterol in a non-aqueous phase system, with a conversion rate of 33% (based on stigmasterol) or 32% (based on ferulic acid).