520 results about "Protein degradation" patented technology

The present invention provides a class of small molecule compounds for targeted degradation of a pan-KRAS protein, a preparation method therefor, and use thereof as a therapeutic agent for preventing and / or treating cancer. The compound of the present invention can effectively degrade and / or inhibit the pan-KRAS protein in cells, and can be used for preparing a drug for treating and / or preventing related diseases or disorders caused by pan-KRAS mediation.

The invention provides a recombinant XVII type collagen and application thereof, and relates to the technical field of protein engineering. The novel recombinant human XVII type collagen is obtained by optimizing and screening collagen structural domain sequences of the human XVII type collagen and then combining the sequences. The recombinant human XVII type collagen is consistent with the corresponding part of the amino acid sequence of the human XVII type collagen, does not generate immunological rejection when being applied to a human body, and can be widely applied to the industries of surgical medical treatment and medical beauty. In addition, the recombinant human XVII type collagen is high in stability, and the problem of protein degradation in the process of expressing recombinant protein by pichia pastoris can be avoided. In addition, the recombinant human XVII type collagen also has the effects of high biological activity, high biological safety, promotion of cell proliferation and differentiation and promotion of hair growth, and can be applied to the field of cosmetics or medicines as a functional component.

The invention discloses an enzyme response type KRAS targeted protein degradation chimera as well as a preparation method and application thereof, and belongs to the technical field of tumor targeted therapy. The enzyme response type KRAS targeted protein degradation chimera disclosed by the invention is obtained by covalently linking three parts, namely a KRAS targeted protein degradation chimera, an enzyme response type amino acid sequence and a cell penetrating peptide amino acid sequence, wherein the KRAS targeted protein degradation chimera is obtained by linking a KRAS targeted peptide and a VHL E3 ligase ligand through succinic acid. The enzyme response type KRAS targeted protein degradation chimera releases the KRAS targeted protein degradation chimera under the action of ATG4 enzyme shearing, and shows a relatively strong lung cancer resisting effect in vitro and in vivo. The invention has significant advantages in the aspect of antitumor drugs, and opens up a new field for the development of targeted protein degradation chimera drugs. Enzyme response type KRAS targeted protein degradation chimera molecular structural formula as follows: # imgabs0 #

According to the GPX4 protein degradation agent and the application, the degradation agent serves as molecular glue to induce tumor cell ferroptosis and is different from an existing PROTAC technology, and the molecular glue can induce interaction between E3 ubiquitin ligase and target protein GPX4 and promote ubiquitination of the E3 ubiquitin ligase and the target protein GPX4. Compared with the existing GPX4 degradation agent, the molecular glue has the advantages of small molecular weight, high cell permeability and better druggability. The GPX4 molecular glue disclosed by the invention can be used for effectively degrading GPX4 and has a killing effect on various tumor cell lines. The preparation method is simple in synthesis route and mild in reaction condition, can be used for being developed into a new generation of GPX4 targeting drugs, and has great clinical application value and considerable market potential.

The invention belongs to the field of food processing, and particularly relates to an ostrich meat preservative and a preservation method. The ostrich meat preservative provided by the invention is prepared by matching and mixing the chitosan, the nisin and the tea polyphenol according to a specific proportion, so that the refrigeration refreshing time of the ostrich meat treated by the preservative can be effectively prolonged, the ostrich meat can maintain a relatively high L * value and a * value within 16 days of storage, the deterioration of meat color is delayed, the water-retaining property is remarkably improved, and the quality of the ostrich meat is improved. The content of thiobarbituric acid reactants and volatile basic nitrogen is obviously reduced, and fat oxidation and protein degradation are inhibited; the total number of bacterial colonies and the number of microorganisms such as coliform bacteria, pseudomonas, mould and saccharomycetes are obviously reduced. The growth and reproduction of putrefying bacteria can be effectively inhibited, and the cold fresh shelf life is prolonged.

The present invention provides compounds, compositions thereof, and methods of using the same for the targeted degradation of proteins, and the treatment of target protein-mediated disorders.

The invention provides a cell protein degradation platform based on an artificial biological macromolecular aggregate. Specifically, the invention provides a PROTAC functional module based on an interworking nucleic acid skeleton, a PROTAC-aggregate complex (MLO-PROTAC), a kit, application and a preparation method of the PROTAC functional module, the PROTAC-aggregate complex (MLO-PROTAC) and the kit, and also provides a targeted protein degradation method. In a PROTAC platform built by the PROTAC functional module and the PROTAC-aggregate complex, a programmable nucleic acid component is used as a core assembly unit, and the functional module is enriched and spatiotemporal-spatial regulation is performed by using the polypeptide aggregate, so that the delivery efficiency and the cytoplasm exposure degree are remarkably improved while the universality is maintained, and the delivery efficiency and the cytoplasm exposure degree are remarkably improved. Therefore, a more effective target protein degradation way is provided for the field.

The invention relates to the technical field of biological medicines, in particular to application of an EIF3A inhibitor in preparation of a medicine for treating hepatic fibrosis. The EIF3A inhibitor relieves the hepatic fibrosis process by inhibiting EIF3A expression of hepatic tissue, relieving endoplasmic reticulum stress, inhibiting an NF-kappa B inflammation pathway and reducing pathological damage of hepatic cells, and the EIF3A inhibitor can be selected from a medicine for knocking down or knocking out EIF3A, a medicine for inhibiting EIF3A protein synthesis or a medicine for promoting EIF3A protein degradation. New mechanism research is provided for occurrence and development of hepatic fibrosis, hepatic cell damage and inflammation can be relieved through targeting EIF3A, hepatic fibrosis related pathological phenotypes are relieved, the protection and treatment effects are achieved, safety is higher, and therefore the application has good practical application value.

The invention provides an anti-freezing denaturation agent for golden and tiger hybrid spotted fish meat protein and a preparation method of the anti-freezing denaturation agent. The invention relates to an anti-freezing denaturation agent for protein of Jinhu hybrid spotted fish. The anti-freezing denaturation agent is prepared from the following raw materials in parts by weight: 5 to 8 parts of trehalose-mannitol, 0.5 to 1 part of nano chitosan, 0.2 to 0.5 part of rosmarinic acid and 0.1 to 0.2 part of polysorbate-80. The trehalose-mannitol is prepared from trehalose and mannitol. Aiming at the characteristics of Jinhu hybrid spotted fish meat, trehalose-mannitol, nano chitosan, rosmarinic acid and polysorbate-80 are taken as raw materials and compounded to obtain a new formula of the protein anti-freezing denaturation agent for the Jinhu hybrid spotted fish meat, and the anti-freezing denaturation agent prepared by adopting the formula and the process disclosed by the invention can be used for inhibiting protein degradation and improving the anti-freezing denaturation effect of the Jinhu hybrid spotted fish meat. The decrease range of MP protein concentration, MP total sulfydryl content and MP Ca < 2 + >-ATPase activity of the antifreeze agent is obviously reduced, and the effect of the antifreeze agent is superior to that of a commercially available antifreeze agent. Moreover, the anti-freezing denaturation agent for the protein of the Jinhu hybrid spotted fish does not contain phosphorus, and has the advantages of safety and high efficiency.

The invention belongs to the technical field of biological medicine, and particularly relates to an LYTAC molecule for targeted degradation of GPC3 and a preparation method and application of the LYTAC molecule. The LYTAC molecule is composed of a target TfR1 nucleic acid aptamer and a target GPC3 nucleic acid aptamer, wherein the nucleotide sequence of the targeted TfR1 nucleic acid aptamer is as shown in SEQ ID NO: 1; the nucleotide sequence of the targeted GPC3 nucleic acid aptamer is as shown in SEQ ID NO: 2. According to the present invention, the research results show that the GPC3 protein content is not affected by the single TfR1 nucleic acid aptamer or the GPC3 nucleic acid aptamer, and the LYTAC molecule can significantly reduce the GPC3 protein content on the surfaces of Hep3B and HepG2 cells. The LYTAC molecule induces GPC3 protein degradation through a lysosome way, then proliferation and migration of liver cancer cells are inhibited, liver cancer treatment is achieved, and the LYTAC molecule has wide application prospects.

The present disclosure relates to harnessing endosomal sorting of lipids to enable targeted protein degradation via the lysosomal degradation pathway. Accordingly, provided herein are molecules for degrading target proteins, pharmaceutical compositions of such molecules, and methods of making and using such molecules.

The present invention relates to a novel compound selected from a protein degrader or conjugate including a PI3K target moiety and an HSP90 target moiety linked through a linker, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof. The compound can treat cancer through a degradation pathway of a heat shock protein conjugate.

The invention discloses a nanoparticle for targeted protein degradation and a degradation method. The nanoparticles can enhance uptake of cells and effectively encapsulate specific antibodies for recognizing target proteins, and meanwhile, the interferon component can induce expression of TRIM family proteins in the cells. After ingestion into the cell, the antibody released by the nanoparticle can bind to the target protein and bind to the TRIM family protein to mediate degradation of the target protein. In this process, although the TRIM family protein is continuously consumed, the TRIM family protein can be compensated by the TRIM family protein expression induced by the particle of the invention, thereby maintaining efficient degradation.

The invention discloses a degradation agent based on indole group fusion covalent warheads and a preparation method and application thereof, and relates to the technical field of drug development, the structural formula of the degradation agent is as follows: R is a single bond or-NH-; a single bond, a, a, a, or a; and is-NH-, or; or; r1 and R2 are respectively and independently-H,-F,-Cl,-Br,-CH3,-OCH3,-NO2,-CH2-O-Ph or-CN; ph is phenyl; and a connection site is represented. According to the invention, an E3 ubiquitin ligase ligand is constructed by using an indole skeleton and acrylate, and then the E3 ubiquitin ligase ligand is connected with a BRD4 protein inhibitor JQ1 through a linker, so that a series of degradation agents based on indole group fusion covalent warheads are obtained, and targeted degradation of BRD4 protein is realized while an E3 ubiquitin ligase ligand library and a protein degradation targeted chimera molecular library are enriched.

The present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein.

The invention relates to the technical field of biological medicine, in particular to an mRNA vaccine based on a protein degradation technology. The mRNA vaccine comprises an mRNA system and a lipid nanoparticle. The mRNA system refers to two mRNAs which can respectively encode an antigen-docking module and a recognition module-E3 ubiquitin ligase binding domain, the E3 ubiquitin ligase binding domain recruits an E3 ubiquitin ligase complex, the antigen is ubiquitinated and degraded into a peptide fragment by utilizing specific binding between the recognition module and the docking module, the peptide fragment is recognized by an MHC-I complex, and the E3 ubiquitin ligase binding domain is used for identifying the MHC-I complex. Then, the body immunity is activated, and the anti-tumor effect is realized. Besides, the invention provides a universal mRNA vaccine, that is, theoretically, different diseases can be treated only by replacing antigens in an mRNA system, the research and development time of the vaccine is greatly shortened, the research and development cost is reduced, a new thought is provided for tumor treatment, and the mRNA vaccine has a huge application prospect.

The invention belongs to the technical field of biological medicines, and relates to a protein degradation system based on polyamide-amine dendrimers as well as a preparation method and application of the protein degradation system. The protein degradation system is of a nano-particle structure, and the nano-particle structure comprises silicon dioxide nano-particles and a polyamide-amine type dendritic polymer layer coating the surfaces of the silicon dioxide nano-particles. An MDM2 protein ligand, a GLUT1 protein ligand and an E3 ubiquitin enzyme ligand are connected to the polyamide-amine dendritic polymer layer through chemical bonds. The protein degradation system provided by the invention can be used for synergistically degrading the MDM2 protein and the GLUT1 protein. The synergistic degradation strategy not only can effectively inhibit proliferation and energy metabolism of tumor cells, but also can significantly enhance the stability of the p53 protein. By recovering the normal function of the p53 protein, the growth of tumor cells is further inhibited, and a new strategy is provided for tumor treatment.

The invention relates to the field of optogenetics, in particular to an optogenetics tool for light-operated induced protein degradation and a construction method and application of the optogenetics tool. The invention relates to an optogenetics tool for light-operated induced protein degradation, which is characterized by comprising a fusion system of a truncated body mTRIM211-80 of mTRIM21 and CRY2, the base sequence of the mTRIM211-80 is as shown in SEQ ID NO. 1 (sequence identifier number 1); the base sequence of the CRY2 is as shown in SEQ ID NO. 2. The optogenetics tool is used for inducing the TRIM21 to form a polymer by utilizing the blue light photosensitive protein CRY2 and is used for the targeted regulation and control of the protein degradation under the driving of the blue light. Targeted degradation of protein can be achieved by utilizing Intrabody (intracellular antibody), time and space targeting is achieved, and after an optogenetics toolbox is optimized, the sensitivity and the reaction rate of the optogenetics toolbox are further improved.

The invention discloses a protein degradation agent compound as well as a preparation method, a pharmaceutical composition and application thereof. The structure of the compound is shown in a formula I, the compound further comprises a deuterated compound, pharmaceutically acceptable salt or a mixture of the deuterated compound and the pharmaceutically acceptable salt, and the compound can effectively degrade MLKL protein on the nanomolar concentration level and achieve anti-necrotic activity on tumor cells and has application prospects as an anti-necrotic apoptosis active molecule. Meanwhile, the preparation method of the compound is convenient and suitable for various structure types.

The invention discloses an aquatic product breeding feed capable of improving flavor and a preparation method thereof, and particularly relates to the technical field of breeding feeds, the feed comprises fish meal, soybean meal, soybean protein concentrate, shrimp meal, chicken meal, wheat flour, cuttlefish paste, phospholipid, grease, mineral substances, vitamins, lettuce polyphenol, an antioxidant, a mildew preventive and the like. Wherein the lettuce polyphenol is a key functional component. The preparation method comprises the following steps: pretreating the raw materials, mixing step by step, adding grease by spraying, tempering, granulating, drying, screening, spraying the antioxidant and the like. The lettuce polyphenol regulates and controls an mTOR signal channel to promote flavor amino acid deposition and inhibit protein degradation, meanwhile, the intestinal microecology is improved, the antioxidant capacity and digestive enzyme activity are enhanced, and the content of flavor substances such as glutamic acid and glycine in aquatic products is remarkably increased. The method is suitable for culturing various aquatic products, and can effectively improve the flavor and quality of the cultured aquatic products.

The invention relates to the field of protein, in particular to a preparation method of recombinant human albumin and a product thereof. The preparation method comprises the following steps: constructing recombinant engineering bacteria which can silence or weaken the expression of one or more genes of PEP4, YPS1, MKC7, PRC1 and PRB1 through a gene editing technology while expressing recombinant human albumin, and silence or weaken the expression of one or more genes of PMT1, PMT2 and PMT4 at the same time; and then, carrying out low O-glycosylation fermentation culture on the obtained engineering bacteria, and carrying out separation and purification to obtain a high-purity recombinant human albumin product. According to the present invention, the protein degradation and the O-glycosylation pathway are cooperatively regulated, and the specific fermentation process is combined, such that the yield of the obtained recombinant human albumin is significantly improved, the characteristics of low immunogenicity and low glycosylation level are provided, and the performance optimization and the clinical application expansion of the recombinant human albumin product can be significantly promoted.

The invention discloses application of an NR1D1 protein phosphorylation site in preparation of cerebral hemorrhage treatment drugs, and belongs to the technical field of molecular biology. According to the invention, the specific phosphorylation site and phosphorylation modification level of the NR1D1 protein are determined for the first time, and the NR1D1 protein can be used as a key marker for evaluating the secondary nerve injury degree of the hemorrhagic cerebral apoplexy and developing treatment and / or alleviation of the hemorrhagic cerebral apoplexy; a specific antigen peptide and an antibody for accurately detecting the NR1D1 protein phosphorylation site are further constructed, and an efficient tool is provided for molecular evaluation of hemorrhagic stroke secondary nerve injury; meanwhile, polypeptide molecules capable of inhibiting NR1D1 protein phosphorylation are researched and developed, through the dual effects of specifically blocking the phosphorylation process and reducing protein degradation, necrosis of brain tissues around hematoma after hemorrhagic cerebral apoplexy is relieved, secondary dyskinesia is improved, and the effect of inhibiting NR1D1 protein phosphorylation is achieved. And a brand new scheme is provided for molecular evaluation and targeted intervention of hemorrhagic stroke secondary nerve injury.

The invention discloses a degradation agent based on benzimidazole fused covalent warheads as well as a preparation method and application of the degradation agent, and relates to the technical field of drug development. The structural formula of the degradation agent based on the benzimidazole fused covalent warhead is shown in the specification, wherein, is phenyl or substituted phenyl; r is methyl or tertiary butyl; the structure is selected from one of the following structures:,,,,,,,,, and; and a connection site is represented. According to the invention, a series of degradation agents based on benzimidazole fused covalent warheads are obtained by utilizing the modular design of a benzimidazole guiding group and an acrylate covalent warhead and then connecting with a BRD4 protein inhibitor JQ1 through a connexon. The degradation agent based on the benzimidazole fused covalent warhead can target the BRD4 protein and efficiently degrade the BRD4 protein. Therefore, targeted degradation of the BRD4 protein is realized while a protein degradation targeted chimera molecular library is enriched.

The subject matter described herein is directed to antibody-CIDE conjugates (Ab-CIDEs), to pharmaceutical compositions containing them, and to their use in treating diseases and conditions where targeted protein degradation is beneficial.

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 relates to the technical field of food processing, in particular to a chicken quality preservation treatment method based on sectional regulation, which is characterized in that chicken is pretreated by a composite biological preservative solution, and ice storage treatment and staged storage are combined, so that microbial growth and enzymatic activity of the chicken are effectively inhibited; fat oxidation and protein degradation are delayed, so that the chicken still keeps excellent quality in long-term storage; in the staged storage process, key indexes are monitored in real time or periodically, a threshold value comparison and stage switching mechanism is established, and accurate dynamic regulation and control of the staged modified atmosphere packaging environment under the condition of dynamic deterioration of the chicken quality are achieved. Through segmented regulation and control, juice loss, color deterioration and decay of the chicken in the storage process can be effectively prevented, so that the sensory quality and the nutritional quality of the chicken are maintained, and meanwhile, the gas utilization efficiency in the storage environment is also remarkably improved.

The present invention provides compounds, compositions thereof, and methods of using the same for the targeted degradation of proteins, and the treatment of target protein-mediated disorders.

The invention relates to a biomarker applied to early diagnosis of sepsis. The biomarker is a fibrous protein degradation product FDP / D-dimer ratio. Compared with a single index (such as PCT, D-dimer), the biomarker has the advantages that the influence of individual difference and detection error can be reduced, and the stability of a result is improved; in combination with clinical information (such as infection evidence), the ratio can be used as an independent or joint index to assist an existing scoring system (such as SOFA) in improving diagnosis accuracy.

The invention discloses a bifunctional molecule compound for inducing SHP2 protein degradation based on a DCAF16 ligand as well as a preparation method and application of the bifunctional molecule compound, belongs to the technical field of medicines, and relates to a bifunctional molecule for inducing SHP2 protein degradation based on the DCAF16 ligand as shown in a general formula (I) or pharmaceutically acceptable salt of the bifunctional molecule, and a pharmaceutical composition containing an SHP2 protein targeted degradation agent. The invention also relates to a preparation method of the compound and application of the compound in preparation of medicines for treating SHP2-mediated tumors and / or other diseases.