360 results about "Protein degradation" patented technology

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 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 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 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 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 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 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.

The invention relates to a Pan KRAS protein degradation agent as well as a preparation method and application thereof. Specifically, the compound provided by the invention has a structure as shown in a formula I. The invention also discloses a preparation method of the compound and application of the compound in prevention and / or treatment of KRAS mutation related diseases.

1. A compound of formula (I): [MCL-1 ligand site]-[linker]-[ligase ligand site] (I), or a salt, solvate, hydrate, isomer, or prodrug thereof, wherein [MCL-1 ligand site] is a compound of formula (A), or [MCL-1 ligand site] is a compound of formula (A1), (A2), (A3), or (A4), and use thereof in the treatment of cancer. [Formula 1] JPEG2025540970000791.jpg126170

Disclosed herein are multifunctional polypeptides comprising an optional signal peptide sequence, a cell penetrating peptide, an antigen binding domain (e.g., anti-synuclein, anti-tau, anti-huntingtin), and a programmable proteasometargeting PEST motif, and methods for using these polypeptides in treatment of protein aggregation diseases, e.g., neurodegenerative diseases.

This invention relates to the field of nanomedicine delivery systems, specifically to an ultrasound-enhanced synergistic immunotherapy drug delivery system, its preparation method, and its applications. The ultrasound-enhanced synergistic immunotherapy drug delivery system includes a lipid shell and a fluorocarbon gas encapsulated within the lipid shell. The lipid shell is made from cancer cell membranes and a lipid membrane formed from synthetic phospholipids. The lipid shell integrates a protein degradation-targeting chimera for degrading PD-L1. This invention combines targeted drug delivery, PD-L1 targeted degradation, and ultrasound enhancement technology to construct an integrated synergistic immunotherapy drug delivery system. Through multi-mechanism synergistic action, it overcomes the bottlenecks of existing PROTAC delivery systems, achieving a highly efficient anti-tumor immune response. This technical solution solves the technical problems of limited tumor tissue penetration and cellular uptake efficiency of PROTAC degrading agents targeting PD-L1, resulting in unsatisfactory delivery effects and promising prospects for widespread application.

The invention provides a targeted degradable protein and application thereof, and belongs to the technical field of biological medicine. The amino acid sequence of the targeted degradation protein is SEQ ID NO.1. When the targeted degradation protein is used for treating breast cancer, target protein degradation can be directly mediated, so that the effect of the target protein is weakened fundamentally, the targeted degradation protein only needs to be combined with the target protein with very strong affinity, specific epitopes do not need to be combined, the design difficulty is low, and the number of adaptive targets is large. Therefore, the targeted degradation protein provided by the invention takes the membrane molecule with high expression of tumor specificity as the effect protein, so that the dual effects of tumor targeting and mediated endocytosis are realized.

The invention relates to the technical field of protein extraction, in particular to a high-content earthworm protein extraction method and device.The extraction method comprises the following steps that S1, a fluid-state protein protective agent and a granular-state protein protective agent are sequentially added into smashed live earthworms, and mixed powder is obtained; s2, water is added into the mixed powder for centrifugation, and supernate is obtained; s3, performing enzymolysis and filtration on the supernate; s4, the filtrate is subjected to activated carbon adsorption and freeze drying, and earthworm protein is obtained; the equipment sequentially comprises a pretreatment chamber, a centrifugal cylinder, an enzymolysis adsorption chamber and a freeze-drying chamber from left to right, according to the extraction method, the protein protective agent is immediately added after the earthworms are crushed, and protein degradation is prevented and protein integrity and biological activity are maintained by inhibiting endogenous protease activity and chelating metal ions; and the protein protective agent maintains the structural stability of the substrate, so that the subsequent enzymolysis is more sufficient, and the protein yield is improved.

Compounds of Formula (IA) (Targeting Moiety)-(Linker)-(Protease Ligand) (IA), where the targeting moiety is an oligonucleotide capable of binding a target protein and the protease ligand is a ligand capable of binding a protease, and methods for the use thereof are provided. Also provided are compounds of Formula (IB) (Targeting Moiety)-(Linker)-(Protease Ligand or E3 Ligase Ligand) (IB), where the targeting moiety is an oligonucleotide capable of binding a target protein, the protease ligand is a ligand capable of binding a protease, and the E3 ligase ligand is a ligand capable of binding an E3 ligase, and methods for the use thereof are provided.

The application discloses a compound capable of inducing SOS1 protein degradation, a preparation method and purposes, and the structure of the compound is shown as formula I. The compound of the application can induce SOS1 protein degradation, is used as a SOS1 degrading agent, and is used for preventing and / or treating tumors. The SOS1 protein ligand-connecting group L-E3 ligase ligand (I).

A compound including formula (I) or formula (II) for use in promoting targeted protein degradation.

The invention belongs to the technical field of medicine. The invention discloses a protein degradation targeting chimera, a pharmaceutical composition taking the protein degradation targeting chimera as an active ingredient, and application of the protein degradation targeting chimera in preparation of drugs for preventing or treating FGFR kinase mediated diseases or symptoms. Specifically, the invention relates to a compound shown as a formula (I), pharmaceutically acceptable salts, stereoisomers or solvates thereof, and a pharmaceutical composition containing the compound, and R1, R2, R3, L and E are described in the specification.

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.

This invention relates to DNA extraction methods from soil and sediments with high humic substances content. The method focuses on the soil preparation phase; removing salts and cations with two different Tris-EDTA (TE) buffers, followed by precipitating humic substances with aluminum hydroxide solution and washing again with TE and cell lysis phase; urea is used as denaturing agents for the cell lysis phase and protein degradation phase while preventing the rediffusion of humic substances with CTAB. The purification can be performed following both the classic phenol chloroform method and using commercial DNA purification columns. This method is very accessible with operation time varying from 1h40 min to 2h30 min. The invention involves the use of TE and aluminum hydroxide solutions for soil preparation, and urea and CTAB as denaturing agents during cell lysis, in the specified concentrations, order, and incubation time, to prevent contamination of final DNA with humic substances

The invention belongs to the field of animal feeding, and particularly relates to application of bacillus megatherium in preparation of fermented feed for reducing methane emission of mutton sheep, the bacillus megatherium is preserved in the China General Microbiological Culture Collection Center on December 6, 2004, and the preservation number is GMCCNo.1259. The invention also provides a fermented feed for reducing methane emission of mutton sheep, the degradation rate of straw rumen dry matter and crude protein can be remarkably increased, the ammonia nitrogen content in the feed is remarkably reduced, and the lactic acid bacteria content is remarkably increased.

An isolated peptide for regulating intracellular protein degradation that includes a linker sequence fused to a C-end degron peptide and, optionally, a caging molecule bonded to the carboxyl group of a C -terminal alanine residue. Also disclosed is a method for temporal control of protein degradation that relies on fusing a protein of interest at its C- terminus to the degron peptide having a caging molecule, and a method for high-fidelity gene editing that utilizes an RNA-dependent endonuclease modified at the C -terminus with the caged isolated peptide. A fusion protein for high-fidelity gene editing is further provided.

The invention discloses an engineered protein and application thereof in mediating non-ubiquitination degradation, and belongs to the technical field of biological medicine. The structural domains CATCH1 and CATCH2 of the MIDN protein and the region between the structural domains CATCH1 and CATCH2 are modified for the first time, the modification mode comprises the steps that the structural domains CATCH1 and CATCH2 and the region between the structural domains CATCH1 and CATCH2 are replaced with antibodies or polypeptides, then structure or sequence optimization is conducted on the basis, and the obtained MIDN engineered protein not only retains the proteasome binding capacity of MIDN, but also has the advantages of being capable of improving the protein quality and the like. According to the present invention, the MIDN-based target protein degradation system has the MIDN-based target protein degradation system, can expand the target range to the membrane protein or the cytoplasm protein, can improve the degradation efficiency of the MIDN-based target protein degradation system, further has the antibody-mediated target protein specificity so as to achieve the pathological / physiological protein distinguishing effect, and does not have the obvious toxicity; therefore, the engineered protein provided by the invention has a good application prospect.