31 results about "Protein phosphorylation" patented technology

The invention belongs to the technical field of biological detection, and relates to an antibody composition aiming at human pS129-alpha-Syn protein detection and application thereof, and the antibody composition comprises a targeted pS129-alpha-Syn protein phosphorylation antibody and a targeted human alpha-synuclein N-terminal antibody. Meanwhile, based on the antibody composition for detecting the human pS129-alpha-Syn protein, the invention further provides a kit for early diagnosis of the Parkinson's disease. The invention provides an antibody composition aiming at human pS129-alpha-Syn protein detection and application of the antibody composition. The antibody composition is higher in detection specificity and sensitivity.

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 provides a method for detecting genes related to early growth traits of Inner Mongolia down producing goats based on copy number variation (CNV). The method comprises the following steps: acquiring whole genome re-sequencing data of 461 Inner Mongolia down producing goats; the method comprises the following steps: detecting autosomal CNV by using CNV native software, and screening out 26,003 non-redundant CNV which covers 1, 015.4 Mb (38.97%) of an autosomal genome; gWAS analysis is carried out on the basis of CNV, 11 CNVs obviously related to early growth traits (birth weight CSZ, weaning weight DRZ, daily gain ADG before weaning and 12-month-old weight ZWT) are identified, and two CNVs influence ADG and DRZ at the same time; seven key candidate genes (ZN845, SOX15, FGF11, GPS2, DVL2, SPRY4 and STAT2) are analyzed and identified through bioinformatics, and GO and KEGG function enrichment analysis is utilized to find that the genes participate in biological pathways such as cell proliferation, differentiation and protein phosphorylation. The invention provides a theoretical basis for molecular marker-assisted breeding of Inner Mongolia down producing goats, and has important scientific value and application prospect.

The present invention discloses a protein phosphorylation site prediction method based on federated learning, which relates to the field of bioinformatics analysis technology, including: each client participating in federated learning pre-processes its protein sequence data and establishes its own training set and test set; each client uses a local data set to train a model and outputs the local model, prediction accuracy and local data set feature description to the committee; the committee tests the local models of each client, selects a local model that meets the standards, and optimizes the aggregated global model based on the feature description of each client data set; uses the fixed members of the federated learning committee to test the aggregated global model and determine whether to end federated learning. Therefore, the above-mentioned protein phosphorylation site prediction method based on federated learning can overcome the problem of data imbalance, effectively protect data privacy, and realize the sharing and utilization of multi-party data.

The present application relates to a kind of FOXM1 protein phosphorylation modification interfering peptide and its application, belong to the field of biological medicine technology. Specifically, the present application is found in research, the transcriptional activity of FOXM1 protein depends on the condensate formed by its polymerization, destroying the polymerization of FOXM1 can effectively inhibit the occurrence and development of tumor, and the phosphorylation of the 376th amino acid of FOXM1 protein can also inhibit polymerization to some extent, thereby inhibiting the transcriptional activation of FOXM1 protein. Therefore, the present application designs an interfering peptide, and introduces phosphorylation modification in appropriate position, obtains a kind of phosphorylation modification interfering peptide FIP4 targeted to FOXM1 protein polymerization domain, the interfering peptide plays a significant role in inhibiting the transcriptional activation of FOXM1 protein in cell and animal in vivo, and can be used for treating tumor-related diseases.

This invention provides novel small molecule non-ubiquitin proteolysis targeting chimera NuTAC, which degrades any selected proteins by directly tethering to the proteasome, processes for the preparation thereof, and its uses in medicine. This invention particularly provides NuTAC molecules with a binder of the proteasomal substrate receptor Rpn13 and a binder of the target protein PD-L1 or BRD4 to induce degradation of target proteins and suppress tumor growth. Also provided are an Rpn13 binder as well as an inhibitor RPI-5, which additionally induces phosphorylation of Rpn13, Src-3 and FBXO2, and another Rpn13 binder NuL1 that does not induce phosphorylation of above proteins. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating and / or preventing diseases (e. g., cancers), and methods of developing reagents to deplete cellular proteins.

This invention discloses the application of Panax notoginseng saponin Ft1 as a plant immune inducer in the control of bacterial plant diseases, belonging to the field of biopesticide technology. This invention is the first to discover that Panax notoginseng saponin Ft1 can effectively activate the plant immune system, promote the expression of the FRK1 immune marker gene, induce reactive oxygen species bursts and calcium ion influx, and activate MAPK protein phosphorylation, thereby enhancing plant resistance to bacterial diseases such as *Pseudomonas syringae*. Unlike other existing Panax notoginseng saponins that directly inhibit fungi as fungicides, Panax notoginseng saponin Ft1 works by activating the plant's own immunity and has no inhibitory effect on plant growth at effective concentrations. It is highly efficient, safe, and environmentally friendly, and can be used as a novel biopesticide for the control of bacterial plant diseases.

The application discloses a method for simultaneously identifying cell subgroups and related factor phosphorylation levels. The method simplifies the protein phosphorylation flow cytometry staining step without affecting the staining effect, can simultaneously detect 17 stained cells, and simultaneously saves cost and is more efficient. The method provided by the application can provide more accurate distinguishing ability, can obtain more information from a small cell sample, can detect abnormal cells at a low level, increases laboratory efficiency, is especially suitable for the research of the immune system, and has a wide prospect.

The present invention discloses a 1-methyl-6-chromenone-indole-2-carboxamide compound, its preparation method, and application. The biologically active 1-methyl-6-chromenone-indole-2-carboxamide nucleus contained in the compound can be further chemically modified to produce a variety of compounds with higher biological activity, expanding the wide application of such compounds in biomedicine and the development prospects of pharmaceutical preparations. At low nanomolar doses, these compounds can significantly inhibit the proliferation of cells such as breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, and diffuse large B-cell lymphoma, and can effectively inhibit STAT3 protein phosphorylation, indicating that these compounds have the potential to be developed as anti-tumor drugs. Furthermore, these compounds can also activate AMPK phosphorylation, indicating that these compounds also have great potential for treating metabolic diseases such as obesity, non-alcoholic fatty liver disease, and diabetes.

The invention discloses a targeted coupled small molecule and a preparation method, a pharmaceutical composition and application thereof. The designed compound can specifically inhibit FGFR in a targeted manner, has anti-proliferative activity to various tumor cells, has low toxicity to normal cells, and can play an anti-tumor effect through various mechanisms such as protein phosphorylation inhibition and DNA damage induction. Meanwhile, the compound also shows the characteristics of high efficiency and low toxicity in vivo, and has a good patent medicine prospect.

The invention belongs to the technical field of stem cell differentiation regulation and control, and particularly relates to a method for inducing SDSCs to be differentiated into PGCLCs by BMP4 through a TGF-beta signal channel and application. The invention provides a method for inducing SDSCs to differentiate into PGCLCs by BMP4 through a TGF-beta signal channel, which comprises the following steps: placing SDSCs in a culture environment containing BMP4, and activating the TGF-beta signal channel to differentiate the SDSCs into the PGCLCs, wherein the activation of the TGF-beta signal channel is shown as the up-regulation of the protein phosphorylation level of SMAD1 / 5 / 8. The invention discloses a complete mechanism that BMP4 induces differentiation through a TGF-beta signal channel, and the BMP4 activates SMAD1 / 5 / 8 phosphorylation and up-regulates ID family transcription factor expression so as to regulate reproductive structure development and chromatin remodeling related target genes, thereby providing a theoretical basis for directional differentiation of stem cells.

The application provides a piperazine-1-methylindole-2-carboxamide compound, a preparation method and application thereof, and belongs to the field of drug synthesis. The piperazine-1-methylindole-2-carboxamide compound has a structural formula as shown in general formula I: wherein R is selected from H, X is O or NH, the piperazine-1-methylindole-2-carboxamide parent nucleus group with biological activity contained therein is further chemically modified to generate a plurality of compounds with higher biological activity, and the application of the compounds in biological medicine is expanded, and the development prospect of the drug preparation is expanded. The compounds can significantly inhibit the proliferation of breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, diffuse large B-cell lymphoma and the like at a low dose (nanomole), can effectively inhibit STAT3 protein phosphorylation, and indicate that the compounds have the prospect of being developed into anti-tumor drugs.

The invention belongs to the technical field of medicine, particularly relates to application of mGluR5 agonist CHPG in preparation of antithrombotic drugs, and proves that the mGluR5 agonist CHPG has an antithrombotic effect for the first time through platelet function detection, activation index analysis, a FeCl3 induced mouse artery injury model and protein phosphorylation detection. Researches show that the mGluR5 agonist CHPG significantly reduces the risk of thrombosis by inhibiting platelet activation, and has an antithrombotic application potential.

The invention relates to an application of STAT3 or a phosphorylation inhibitor thereof in prevention or treatment of silent corticotropin adenoma, and particularly provides an application of STAT3 or a protein phosphorylation inhibitor thereof in prevention and / or treatment of silent corticotropin adenoma. According to the invention, it is found for the first time that a signal transduction and transcriptional activation factor 3 (Signal Transduction and Transcriptional Activator of Of Transcriptional Activator 3, STAT3) and a phosphorylation site of the STAT3 have specific enrichment in silent corticotropin adenoma, and the application of the STAT3 to the silent corticotropin adenoma has the advantages that the specificity of the silent corticotropin adenoma and the phosphorylation site of the silent corticotropin adenoma is improved;

The application provides a 1-methyl-6-pyrazinyl indole-2-carboxamide derivative, a preparation method and application thereof, and belongs to the field of drug synthesis. The structural formula of the 1-methyl-6-pyrazinyl indole-2-carboxamide derivative is shown in general formula I: wherein R1 is selected from the group containing the 1-methyl-6-pyrazinyl indole-2-carboxamide parent nucleus group with biological activity, further chemical modification of the 1-methyl-6-pyrazinyl indole-2-carboxamide parent nucleus group generates a plurality of compounds with higher biological activity, and the application expands the wide application of the compounds in biological medicine and the development prospect of drug preparations. The compounds can significantly inhibit the proliferation of breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, diffuse large B-cell lymphoma and the like at a low dose (nanomole), can effectively inhibit STAT3 protein phosphorylation, and indicate that the compounds have the prospect of being developed into anti-tumor drugs.

The present invention discloses a piperazine-1-methylindole-2-formamide derivative, a preparation method and an application thereof, and belongs to the field of drug synthesis. The piperazine-1-methylindole-2-formamide derivative structural formula is shown in general formula I: wherein R1 is selected from n=1,2,3,4,5,6,7,8,9,10. The biologically active piperazine-1-methylindole-2-formamide nucleus group contained therein is further chemically modified to produce many biologically more active compounds, which expands the wide application of such compounds in biomedicine and the development prospects of pharmaceutical preparations. Such compounds can significantly inhibit the proliferation of cells such as breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, diffuse large B-cell lymphoma at low doses (nanomolar), and can effectively inhibit STAT3 protein phosphorylation, indicating that such compounds have the prospect of being developed as anti-tumor drugs.

The invention discloses application of a CCNB1 phosphorylation inhibition tool in preparation of a medicine for preventing and / or treating triple negative breast cancer, and particularly relates to application of a CCNB1 protein S128 site phosphorylation inhibitor in preparation of a medicine for preventing and / or treating triple negative breast cancer. The phosphorylation inhibitor refers to a tool or means used in the process of blocking or weakening protein phosphorylation, particularly a gene editing system, and the 128 serine Ser coded by a CCNB1 gene is mutated into alanine Ala which is recorded as S128A in a target cell. Compared with a traditional small molecule drug, the gene editing tool accurately intervenes phosphorylation modification at the gene level, has the advantages of being clear in mechanism, high in targeting performance, high in safety and the like, is suitable for basic research and potential clinical transformation of TNBC targeted therapy, and has a good application prospect.

The present invention discloses 1-methyl-6-chromenone-indole-2-carboxamide compounds, their preparation methods, and applications. The biologically active 1-methyl-6-chromenone-indole-2-carboxamide core group contained in these compounds can be further chemically modified to produce numerous compounds with even higher biological activity, expanding the broad application of these compounds in biomedicine and the development of pharmaceutical preparations. These compounds significantly inhibit the proliferation of cells in cancers such as breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, and diffuse large B-cell lymphoma at low (nanomolar) doses, and effectively inhibit STAT3 protein phosphorylation, indicating that these compounds have the potential to be developed as anti-tumor drugs. Furthermore, these compounds can activate AMPK phosphorylation, suggesting that they also have great potential for treating metabolic diseases such as obesity, non-alcoholic fatty liver disease, and diabetes.

A human-derived SIRT6 gene is amplified and cloned to a plasmid vector to construct a pSIRT6 plasmid, and under the action of Sirt6, the proportion of memory CD8 + T cells causing mitochondrial dysfunction after SARS-CoV-2S protein stimulation of a new coronavirus is reduced, so that the number of normal memory CD8 + T cells is increased. A further research shows that the protein phosphorylation levels of PI3K, Akt and mTOR in the CD8 + T cells stimulated by the SARS-CoV-2S protein are inhibited, and the whole phosphorylated protein level in the cells is reduced. For a constructed mouse influenza A virus infection model, the virus load is reduced under the action of Sirt6, the inflammatory response of a mouse lung pathological section is obviously reduced, the generation of memory CD8 + T cells in a mouse PBMC (peripheral blood mononuclear cell) is increased, and the mitochondrial function of the memory CD8 + T cells gradually returns to normal. The invention records that the human STRT6 gene has a remarkable treatment effect on the cellular immune process caused by the new coronavirus and the influenza virus.

The invention relates to an application of LtSCRE11 protein in regulating and controlling resistance of peach trees to gummosis. Micromolecular cysteine-rich protein LtSCRE11 secreted by peach gummosis pathogenic bacteria, namely, dispora pirocolor, is screened by a method of combining a genome and a plant bacterium interaction transcriptome with bioinformatics. It is found through injection of nicotiana benthamiana that LtSCRE11 can induce ROS bursting and callus accumulation, and injection of purified LtSCRE11 protein into nicotiana benthamiana and peaches can induce expression of plant immune related genes and MAPK protein phosphorylation signals, so that resistance of nicotiana benthamiana and peaches to pathogenic bacteria is induced. The invention proves that the LtSCRE11 plays a positive role in coping with the infection of pathogenic bacteria by plants, the resistance of peaches to the pathogenic bacteria of the gummosis can be remarkably improved by injecting the LtSCRE11 protein into leaves of peach trees, and the LtSCRE11 protein is expected to be developed into a novel immune resistance inducer target for preventing and controlling the gummosis of the peach trees.

The invention discloses a 1-methyl-6-aryl indole-2-formamide derivative and a preparation method and application thereof, and belongs to the field of drug synthesis, the structural formula of the 1-methyl-6-aryl indole-2-formamide derivative is shown as a general formula I, in the formula I, R1 is selected from G = C or N; w = C or N; the 1-methyl-6-aryl indole-2-formamide mother nucleus group with biological activity contained in the compound is further chemically modified to generate a plurality of compounds with higher biological activity, so that the wide application of the compounds in biological medicines and the development prospect of medicinal preparations are expanded. The compound can significantly inhibit proliferation of cells such as breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, diffuse large B-cell lymphoma and the like at a low dosage (nanomole), and can effectively activate AMPK protein phosphorylation, which shows that the compound has a prospect of being developed into antitumor drugs.

The invention discloses a method for simultaneously identifying phosphorylation levels of cell subgroups and related factors. According to the method, the protein phosphorylation flow cytometry staining step is simplified, the staining effect is not affected, 17 kinds of stained cells can be detected at the same time, in addition, the cost is saved, and higher efficiency is achieved. According to the method provided by the invention, more accurate distinguishing capability can be provided, more information can be obtained from a few-cell specimen, abnormal cells can be detected at a low level, the laboratory efficiency is improved, and the method is particularly suitable for research of an immune system and has a wide prospect.

The invention relates to an application of dehydrotumuloic acid and / or a salt thereof in preparation of an anti-coxsackie virus drug. It is found that the dehydrotumuloic acid and / or the salt thereof have / has an extremely remarkable inhibiting effect on mRNA expression, virus protein expression and plaque formation of the coxsackie virus, the infection capacity of the coxsackie virus can be reduced, cell infection caused by the coxsackie virus can be inhibited, and therefore the dehydrotumuloic acid and / or the salt thereof have the good anti-coxsackie virus activity. A further research shows that the dehydrotumuloic acid and / or the salt thereof can effectively inhibit activation of key protein phosphorylation in an MAPK signal channel caused by coxsackie virus infection and inhibit virus replication. The good anti-coxsackie virus activity of the dehydrotumoic acid and / or the salt thereof provides an effective scheme for treating coxsackie virus infection and diseases caused by the coxsackie virus infection, and the dehydrotumoic acid and / or the salt thereof can also be used as an effective anti-coxsackie virus lead compound.

The invention belongs to the field of biological medicine, and relates to a medicine for treating pulmonary arterial hypertension and application thereof. The invention provides application of a reagent for promoting tyrosine at a phosphorylation site of protein to be mutated into cysteine at a non-phosphorylation site in preparation of drugs for treating pulmonary arterial hypertension. By adjusting the phosphorylation signal of the amino acid at the phosphorylation site in the protein, the function of the protein is regulated and controlled without influencing other phosphorylation signal pathways of the protein, so that intervention is carried out at the initial stage of an upstream signal formed by disease pathology, and the purpose of treating pulmonary arterial hypertension is achieved.

The invention discloses a D53 protein phosphorylation modification site deletion mutant and application of the D53 protein phosphorylation modification site deletion mutant in regulation and control of plant types. Serine at the 589th site of the protein D53 is mutated into aspartic acid, amino acid sequences at other positions are not changed, the protein D53S589D is obtained, the serine at the 589th site of the protein D53 is mutated into aspartic acid, and the phosphorylation state of the serine at the 589th site of the protein D53 is simulated. Experiments prove that the protein D53 is mutated into the protein D53S589D in a rice genome, that is, the tillering number of rice can be increased by improving the phosphorylation level and / or activity of the 589th serine of the protein D53. The method provided by the invention can directionally improve the tillering character of rice, and has important application value.

The application relates to the technical field of data processing, and discloses a PRAK signal pathway analysis method and system. The method comprises the following steps: collecting circRNA expression profiles, miRNA regulation data and PRAK pathway protein phosphorylation data by high-throughput sequencing technology to form a comprehensive data set, mining molecular interaction relationships to construct a pathway connection matrix containing three regulation axes of P38-PRAK-HSP27, VEGFA-PRAK and PRAK-GTPBP4-RhoA, predicting the PRAK pathway activation strength value by using a graph neural network algorithm, extracting the response characteristic markers of a chemotherapy-resistant type, an apoptosis-sensitive type and a proliferation regulation type, and matching an optimal PRAK pathway intervention target point combination. The application solves the technical problem that the existing PRAK signal pathway analysis method cannot intelligently process multi-omics data and accurately predict the pathway activity state.

The invention relates to the technical field of data processing, and discloses a PRAK signal path analysis method and system. The method comprises the steps that a circRNA expression profile, miRNA regulation and control data and PRAK pathway protein phosphorylation data are collected through a high-throughput sequencing technology to form a comprehensive data set, the molecular interaction relation is mined to construct a pathway connection matrix containing three regulation and control axes of P38-PRAK-HSP27, VEGFA-PRAK and PRAK-GTPBP4-RhoA, the PRAK pathway activation intensity value is predicted through a graph neural network algorithm, and the PRAK pathway activation intensity value is calculated. Chemotherapy drug resistance type, apoptosis sensitive type and proliferation regulation type response feature identifiers are extracted, and the optimal PRAK pathway intervention target combination is matched. The technical problem that an existing PRAK signal channel analysis method cannot intelligently process multi-omics data and cannot accurately predict the active state of the channel is solved.

The present invention discloses a 1-methyl-6-alkynyl indole-2-carboxamide derivative, a preparation method, and an application thereof, belonging to the field of drug synthesis. The structural formula of the 1-methyl-6-alkynyl indole-2-carboxamide derivative is shown in General Formula I: #imgabs0# wherein R1 is selected from #imgabs1##imgabs2##imgabs3#. The biologically active 1-methyl-6-alkynyl indole-2-carboxamide nucleus group contained therein is further chemically modified to produce a variety of compounds with higher biological activity, thereby expanding the wide application of such compounds in biomedicine and the development prospects of pharmaceutical preparations. Such compounds can significantly inhibit the proliferation of cells such as breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, and diffuse large B-cell lymphoma at low doses (nanomolar), and can effectively activate AMPK protein phosphorylation, indicating that such compounds have the prospect of being developed into anti-tumor drugs.

The present disclosure provides for high affinity variants of SH2 domains, methods of manufacturing such compositions, their use in screening, and in methods of their administration. The compositions and methods provided herein can be used for targeting protein phosphorylation of tyrosine residues as a means for identifying markers of pathology for therapeutic interventions.

The invention relates to the field of biological information, and discloses a protein phosphorylation site function evaluation method based on a kinetic model in combination with an artificial intelligence algorithm. Comprising the following steps: S1, acquiring intracellular omics data of cells under N conditions; s2, taking the omics data under each condition as a reference one by one, substituting the data in the S1 into a kinetic model, and estimating model parameters by introducing a Bayesian algorithm; meanwhile, whether a certain protein phosphorylation site has functions or not under the current reference condition is evaluated through likelihood ratio test; and S3, repeating the step S2 for N times until each condition serves as a reference, summarizing the results of a certain protein phosphorylation site under N iterations, and estimating the probability that the potential protein phosphorylation site has a regulation function under N conditions by adopting a maximum likelihood estimation method. According to the method, the model parameter estimation capability of an artificial intelligence algorithm is fully utilized, protein abundance data are integrated, phosphorylation abundance data are also integrated, model solving is more accurate, and false positive occurrence is reduced.