163 results about "Proteolysis" patented technology

The present invention relates to compounds of formula (I) useful for the ex vivo, in vitro or in vivo degradation of BRAF by the ubiquitin proteolysis pathway. The invention also provides pharmaceutically acceptable compositions comprising the compounds, and methods of using the compositions in the treatment of various diseases, disorders, and / or conditions.

The invention belongs to the technical field of bioengineering and application thereof, and particularly relates to a laver compound zymolyte as well as a preparation method and application thereof. The compound enzyme is prepared through a compound enzymolysis process of protease and laver polysaccharide enzyme. Compared with a traditional single proteolysis process, a composite enzymolysis process of adding the high-enzyme-activity laver polysaccharide enzyme effectively breaks a'polysaccharide-protein 'composite structure of laver cell walls, so that the viscosity of zymolyte is reduced, high laver liquefaction rate and high product yield are realized, and the release efficiency of nutritional active ingredients is remarkably improved; the product is rich in low-molecular-weight polypeptide and oligomeric porphyra polysaccharide. The obtained zymolyte shows the comprehensive effects of improving joint activity, inhibiting osteophyte formation, adjusting cartilage metabolism balance and relieving inflammatory response in an osteoarthritis mouse model, and osteoarthritis is effectively relieved. According to the invention, efficient release and utilization of nutritional active ingredients of the laver are realized, and powerful technical support is provided for developing high-valued products, such as health-care products and functional foods, which have the function of maintaining joint health.

Provided herein are compounds of formula (I), or their tautomers, stereoisomers, or pharmaceutically acceptable salts. These compounds are useful as KRAS(G12D) proteolytic agents and / or inhibitors. [Case 1] TIFF2026511222000314.tif64165

The invention discloses a method for synergistically improving the bleeding problem in the storage process of pea starch-quinoa protein gel through proteolysis and gellan gum addition. The invention provides a method for preparing gel. The method comprises the following steps: (1) mixing enzymolysis quinoa protein, pea starch, gellan gum and water to obtain a mixed suspension; and (2) heating and gelatinizing the mixed suspension, and cooling and molding to obtain the gel. The gel prepared by the method has the beneficial effects that the water binding capacity is high, and the bleeding rate is low; microscopic structure observation shows that a highly compact and uniform network is formed, and no obvious bubbles exist; low-field nuclear magnetic resonance analysis shows that the bound water proportion is obviously increased; a dynamic rheological test proves that the gel has excellent gel stability; and the process is simple and safe and easy for industrial production. The invention provides a reliable technical scheme for the development of high-protein nutritional soft food for old people.

Use of glycogen synthase kinase-3 (GSK3) as a protease, and a GSK3-based proteolysis-targeting chimera (PROTAC) and a preparation method and use thereof are provided, belonging to the technical field of proteolysis. The GSK3 and an N-terminal domain, an intermediate domain, or a C-terminal domain thereof have a protease activity and can achieve efficient proteolysis. Based on the GSK3 and other similar proteases, PROTACs can be developed to achieve efficient targeted proteolysis of a target protein.

The present disclosure can improve the degree of soy protein proteolysis and the ability to produce valine, isoleucine, and leucine, which are branched-chain amino acids, as well as other amino acids, such as threonine, glycine, tyrosine, and lysine. Accordingly, the present disclosure can prevent sarcopenia and has antioxidant activity. Also, the present disclosure can maintain protein metabolic balance and relieve sarcopenia by muscle synthesis.The self-aggregation, hydrophobicity, and intestinal adhesion of a mixed strain is improved compared to a case where a single strain used for the mixed strain is used. Therefore, when the mixed strain of the present disclosure is ingested, the strain can remain for a long time in the intestine.

The present application provides a kind of as CDK2 protein degradation agent and its use. Specifically related to the compound shown in formula (I), its tautomer, stereoisomer, hydrate, solvate, pharmaceutically acceptable salt or prodrug and preparation method thereof, and the use in the preparation for treating CDK2 related disease drug.

Disclosed are substituted heterocyclic compounds and proteolysis-targeting chimeric molecules (PROTACs). The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC. The disclosed PROTACs are shown to induce degradation of c-MYC protein. The substituted heterocyclic compounds and proteolysis-targeting chimeric molecules (PROTACs) disclosed, herein may be utilized as therapeutics for treating cancer and cell proliferative disorders.

The invention relates to the technical field of proteolysis, in particular to a microwave-assisted proteolysis device which comprises a sample tray arranged on the inner side of a box body, and the sample tray comprises an upper tray arranged on the inner side of the box body and a lower tray fixed to the bottom of the upper tray. A positioning assembly for synchronously clamping the plurality of enzymolysis tanks and keeping the enzymolysis tanks stable is arranged on the sample tray, and the positioning assembly comprises a plurality of first annular discs arranged on the upper tray and a plurality of second annular discs arranged on the lower tray. The stability of each enzymolysis tank during enzymolysis is ensured, non-uniform microwave heating caused by lateral inclination of the enzymolysis tanks is avoided, the reaction consistency in the enzymolysis process is improved, the proteolysis effect is enhanced, meanwhile, the stable digestion tank position can ensure that each sample reacts under the same condition, and the enzymolysis accuracy is improved. The experimental error caused by non-uniform heating of the sample is reduced, the reliability and the accuracy of the experimental result are improved, and the application range of the enzymolysis device is expanded.

The invention relates to the field of biological fermentation, in particular to a method for efficiently preparing anti-aging ergothioneine through fermentation of compound bacteria combined with bolete and application thereof.The method comprises the steps that halophilic bacillus SC-1, halophilic archaea IR-2 and thermophilic casein dissolving bacteria PC-3 are mixed according to the volume ratio of 1: 1: 1, bolete and pleurotus citrinopileatus are used as raw materials, and a mixture is prepared through fermentation; fermenting for 120 hours in an optimized basic culture medium under the conditions that the temperature is 30 + / -0.5 DEG C, the speed is 150rpm + / -10rpm and the pH value is 5.8 + / -0.2; through a step-by-step process of purifying EGT by using D101 resin and purifying RNET-1 by using DEAE-52 resin, a double-active-component extract is synchronously obtained. Through the synergistic effect of three strains with complementary functions, an efficient system of raw material degradation, carbon source supply, double precursor synthesis and double active component accumulation is constructed, synchronous high yield of ergothioneine and novel antioxidant protein RNET-1 is realized for the first time, and the blank of single active component in the prior art is filled.

The invention discloses a multifunctional special dietary food skin beautifying and shaping formula and application, and belongs to the technical field of beauty treatment. The multifunctional special dietary food at least comprises collagen peptide, collagen tripeptide, skipjack elastin peptide, carob bean extract, phosphatidylserine, casein hydrolytic peptide, nicotinamide, rice bran oil powder, haematococcus pluvialis, cranberry powder, oriental cherry flower powder, pig blood peptide powder, red date peptide powder and cattle spleen peptide. The health-care product can comprehensively supplement nutrition recovered after exercise, has the effects of beautifying, shaping and removing wrinkles, can effectively relieve pressure and regulate emotion, and also has the effects of improving female physiological health, strengthening the spleen and stomach and enhancing immunity.

Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and / or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

The application discloses selenium-containing chickpea peptides, a preparation method thereof and application of the selenium-containing chickpea peptides in preparation of blood pressure lowering drugs, and belongs to the technical field of bioactive peptides. Selenium-enriched Bacillus natto is used to ferment chickpeas to obtain selenium-containing chickpea protein hydrolysate, and then fermentation conditions are optimized and quantitative peptidomics technology is used to obtain selenium-containing chickpea peptides PQM and PQML. Experiments prove that the selenium-containing chickpea peptides have good in-vivo stability, bioavailability and blood pressure lowering activity, have an effect of inhibiting angiotensin converting enzyme (ACE) activity, and have potential for preventing or treating hypertension.

The invention provides an ultrasonic response type microsphere preparation entrapped with a protein degradation agent as well as a preparation method and application of the ultrasonic response type microsphere preparation. The microsphere is of a microsphere structure entrapped with a protein degradation agent and formed by a conjugate of a biodegradable polymer and a sound-sensitive agent and the protein degradation agent. According to the invention, the targeted protein degradation agent is entrapped in a biodegradable novel polymer matrix, so that the slow release effect of the medicine is realized, and the long-acting effect is achieved at a specific part in the body. The microsphere combines the respective advantages of an ultrasonic technology and a targeted protein degradation technology, and the two technologies work together, so that the controllability of drug release is remarkably improved, a synergistic effect is achieved, and the treatment effect is improved.

The present invention relates to enhancement and stabilization of proteolytic activity of proteases. The present invention discloses a method for enhancing and / or stabilizing the proteolytic activity of a protease, characterized in that said method comprises (i) contacting the protease with a reducing agent wherein the cysteine residues of the protease are maintained in the reduced state, (ii) removing substantially all of the oxygen from the area surrounding the protease, and (ii) removing the cysteine residues of the protease from the reducing agent. And (iii) binding the protease to an anionic polymer matrix such that the protease is non-covalently bound to the anionic polymer matrix.

The application discloses an aminopyrimidine compound as a protein degradation agent, which is a compound shown in formula (I) or a pharmaceutically acceptable salt, stereoisomer or solvate thereof. The application also discloses a preparation method and medical application of the compound. The compound has FLT3 and CHK1 degradation activity, has proliferation inhibition activity on various tumor cell strains, is effective on various AML mutations such as internal tandem duplication mutations of a near-membrane domain and D835 point mutations of an activation loop in a kinase domain, can overcome drug resistance caused by point mutations in clinic, and can be applied to preparation of an antitumor drug.

A polypeptide comprising: a) milk-clotting enzyme activity, wherein the C / P ratio of clotting activity (C) to proteolytic activity (P) is equal to or greater than the C / P ratio of a polypeptide having the amino acid sequence of SEQ ID NO: 2; and b) alpha-S1-I casein fragment generating activity that is equal to or greater than the alpha-S1-I casein fragment generating activity of a polypeptide having the amino acid sequence of SEQ ID NO: 2; and / or c) a clotting time at pH 6.1 that is equal to or less than the clotting time of a polypeptide having the amino acid sequence of SEQ ID NO: 2.

The application relates to the field of biotechnology, and discloses a method and system for regulating the ratio of amino acids and peptides after soybean proteolysis, which comprises collecting enzyme-coupling parameters in the whole proteolysis process to generate time series data, obtaining a multi-dimensional dynamic covariance matrix based on the data, identifying significant enzyme interaction through the matrix, and generating a list; a multi-level enzyme interaction network model is constructed according to the list, and finally, dynamic and accurate regulation of the ratio of amino acids and peptides is realized based on the model; the application can effectively solve the identification problem of hidden interaction interference in a multi-enzyme system, improve the consistency and predictability of product functions, and reduce the batch-to-batch fluctuation of the content of target functional peptides.

Orally administered pharmaceutical compositions comprising incretin or its analogues or derivatives are presented, which allow for prolonged glycemic control. The formulations presented herein incorporate a self-emulsifying drug delivery system (SEDDS). Advantageously, such formulations provide protection in the upper gastrointestinal tract from proteolytic conditions while allowing for efficient drug release and absorption in the lower gastrointestinal tract.

The invention discloses an aquatic product phagostimulant based on yeast synergistic enzymolysis soybean meal and enzymolysis fish cream and a preparation method of the aquatic product phagostimulant. The preparation method comprises the following steps: mixing whole soybean meal with high-density yeast liquid, adding a compound enzyme preparation for constant-temperature enzymolysis, and drying after solid-liquid separation to obtain semi-finished soybean meal; adding compound protease into the anchovy fish paste for enzymolysis to obtain enzymolysis fish paste rich in small peptides; and uniformly mixing the two components according to a ratio, and drying at low temperature to obtain the aquatic product phagostimulant. The yeast synergistic enzymolysis and directional proteolysis process is adopted, so that the flavor synergistic effect and the nutritional quality of the product are remarkably improved, and the final product is high in crude protein content, excellent in digestibility, rich in active substances such as flavor nucleotides, small peptides and free amino acids, excellent in food calling effect on aquatic animals and high in quality. The traditional phagostimulant can be replaced, and the feeding enthusiasm is improved.

The invention relates to an isolated peptide having an amino acid sequence selected from the group consisting of: Pro-Val-Leu-Lys (SEQ ID NO: 1); Pro-Leu-Pro-Arg (SEQ ID NO: 2); Glu-Ala-Glu-Phe-Asp (SEQ ID NO: 3); Pro-Glu-Arg-Asn-Glu (SEQ ID NO: 4); Pro-Gln-Pro-Glu-Arg (SEQ ID NO: 5); Glu-Phe-Asp-Glu-Lys-Pro-Ala-Asp (SEQ ID NO: 6); Glu-Asp-Ala-Pro-Val-Leu-His (SEQ ID NO: 7); Glu-Phe-Asp-Ala-Arg-Pro-Thr (SEQ ID NO: 8); Glu-Glu-Thr-Pro-Ser-His-Asp (SEQ ID NO: 9); Glu-Glu-Val-Glu-Glu-Glu-Glu-Val-Glu (SEQ ID NO: 10); Glu-Phe-Asp-Glu-Lys-Ala-Pro-Asp (SEQ ID NO: 11); Glu-Asn-Ala-Pro-Asp-Gln-Lys (SEQ ID NO: 12); Glu-Asp-Met-Ala-Pro (SEQ ID NO: 13); Pro-Ile-Asn-Asp-Asn (SEQ ID NO: 14); Pro-Thr-Asp-Leu (SEQ ID NO: 15); Pro-Val-Ala-Glu (SEQ ID NO: 16); Arg-Asn-Gly-Pro-Arg (SEQ ID NO: 17); Arg-Ala-Glu-Asp-Thr-Ala-Thr-Tyr-Tyr (SEQ ID NO: 18); Glu-Gly-Asp-Ser-Ala-Ala-Ile (SEQ ID NO: 19); Glu-Pro-Glu-Gly-Asp-Val-His-Gln (SEQ ID NO: 20); and Glu-Asp-Glu-Val-Leu-Ala-Thr-Pro (SEQ ID NO: 21), a protein hydrolysate comprising the isolated peptides, and use thereof as a taste-modulating agent in food and pharmaceutical preparations.

This invention relates to the field of food processing technology and discloses a process for preparing plant-based beverages containing casein hydrolysate peptides. The process includes: preheating a base liquid containing casein hydrolysate peptides and anionic polysaccharides and pumping it into a Venturi channel; inducing polysaccharide volume expansion by utilizing the hydrostatic pressure drop in the venturi channel to construct an isolation layer; simultaneously aspirating a low-temperature plant polyphenol extract, using the temperature difference to form an adhesion interface on the surface of the isolation layer; after the mixed fluid enters the expansion section, using the compressive force generated by hydrostatic recovery to press the polyphenols into the polysaccharide gaps, constructing a composite physical isolation phase; and triggering polysaccharide thermal gelation crosslinking by heating to establish a physical barrier. This invention utilizes the microscopic encapsulation mechanism generated by the fluid pressure field and temperature gradient to effectively block contact between polyphenols and protein molecules, inhibit complexation precipitation under thermal shock, and ensure that the beverage system possesses excellent thermal stability and storage stability.

The invention relates to proteases exhibiting proteolytic activity and comprising an amino acid sequence that, over its total length, corresponds to the amino acid sequence specified in SEQ ID NO:1 by at least 70% and increasingly preferably by at least 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94.5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5% and 98% is identical, wherein the protease, with reference to the numbering according to SEQ ID NO:1, has at least one amino acid substitution at at least one of the positions corresponding to positions 97, 3, 99, 127 and 211, which is selected from the group consisting of N97E, R99E, R99I, R99N, R99V, R99T, D127E and M211C. Such proteases are suitable for use in washing and cleaning agents, in particular liquid textile detergents, and exhibit improved cleaning performance compared to a reference protease.The invention further relates to the use of these proteases and processes in which they are used, as well as washing and cleaning agents containing them, in particular liquid textile detergents.

A pro-moiety and a composition comprising a pro-moiety for use in a therapeutically or diagnostically effective amount in a method for detecting and / or treating prostate cancer in a subject is disclosed. The pro-moiety comprises a first peptide, and a second peptide that is linked to the first peptide, wherein the peptide comprises a sequence that is configured near a first terminus for conjugating to a drug to form a prodrug that is rapidly and / or highly selectively cleaved by prostate-specific antigen (PSA), and configured at a second terminus to bind with high selectivity to the active site of PSA, and the second peptide comprises a sequence having a negative charge to slow uptake of the prodrug by cells, and wherein the second peptide is cleaved from the first peptide upon proteolysis by PSA to produce a conjugate of the first peptide and the drug that is suitable for uptake by target cells.

The invention discloses an ATP hydrolase antibody efficient screening method based on a fluorescent probe, the method comprises two detection schemes of a biochemical system and a cell system, in the biochemical system, the antibody inhibition rate is directly calculated by quantifying the residual amount of ENTPD2 protein after ATP hydrolysis; in a cell system, cells over-expressing ENTPD2 are used for verifying the inhibition function of the antibody on transmembrane enzyme. According to the biochemical system method, antibody purification is not needed, primary screening can be completed only through 5-15 microliters of B cell supernate, the screening accuracy is high (the cell system can be used as an antibody obtained through verification and screening), the result is consistent with the in-vivo drug effect result, the method is suitable for development of anti-ENTPD2 antibody drugs, and the research and development cost is remarkably reduced.

An organic solid-state fermentation enzyme formulation and an organic plant protease hydrolysate, and preparation methods therefor. The organic solid-state fermentation enzyme formulation is prepared by solid-state fermentation of protease-producing microorganisms, wherein the organic solid-state fermentation enzyme formulation comprises neutral protease, acidic protease, alkaline protease, glucoamylase, and cellulase. By means of using the protease-producing microorganisms to perform solid-state fermentation on organic plant raw materials, the organic solid-state fermentation enzyme formulation rich in the acidic protease, the neutral protease, the alkaline protease, the cellulase, and the glucoamylase is obtained, and then a small amount of additional enzyme is added in the organic solid-state fermentation enzyme formulation, thereby improving the plant proteolysis efficiency by means of an enzyme system synergistic complementary effect.

The invention provides for a screening assay-using a selective proteolysis of recombinant full-length PIKfyve at an endogenous caspase 3 cleavage site to liberate the 34 kDa C -terminal kinase domain. Despite instability of the kinase domain to isolation, the liberated kinase domain is stable in the presence of the N-terminal PIKfyve protein fragment and can thus be treated with compounds of interest and analyzed by mass spectrometry, such as RapidFire-MS, with each injection taking under one minute. The assay was established to triage small molecules for covalent modification of PIKfyve. The assay was also established using cysteine-mutant proteins, where the reactive cysteine was replaced with an inert amino acid which when run through the same experimental protocol, was used to confirm adduct formation at the target cysteine.

The present invention relates to a genetically modified plant or plant cell derived from a wild-type plant or plant cell, said wild-type plant or plant cell producing at least one serine protease comprising the motif SSRGPX1LKPDX2X3APGX4SGTSMSCPHX5PX6WSPX7AX8X9SAX10MTT (SEQ ID No. 1), whereinX1 is a peptide consisting of 7 amino acid residues, X2 is I or L, X3 is T or M, X4 is a peptide consisting of 27 or 28 amino acid residues, X5 is a peptide consisting of 12 amino acid residues, X6 is T or E, X7 is S or A, X8 is V or I, X9 is K or R and X10 is I or M, wherein the proteolytic activity of the at least one serine protease in the genetically modified plant or plant cell is reduced compared to its activity in the wild-type plant or plant cell, wherein the genetically modified plant or plant cell comprises at least one exogenous nucleic acid molecule encoding for at least one protein or polypeptide of interest.

The invention discloses a pentapeptide VE5 with xanthine oxidase inhibitory activity and a preparation method and application thereof, and belongs to the technical field of small molecule peptides. The amino acid sequence of the pentapeptide VE5 is VSIVE, and the pentapeptide VE5 can be prepared through a solid-phase synthesis method and an enzymolysis method. The pentapeptide VE5 is identified from porphyra haitanensis proteolysis liquid and has potential interaction with xanthine oxidase, under the concentration of 0.1 mg / mL, the xanthine oxidase inhibition rate is 67.88%, and compared with goose carnosine (the xanthine oxidase inhibition rate is 36.03%), the xanthine oxidase inhibition rate is remarkably increased (plt; and the compound has higher xanthine oxidase inhibitory activity, and can be used for preparing a preparation for inhibiting xanthine oxidase activity and relieving hyperuricemia.

Provided are a PROTAC compound targeting estrogen receptor (ER) proteolysis and uses thereof.