52 results about "Posttranslational modification" patented technology

The invention belongs to the technical field of medical diagnosis, and discloses a quantum multicolor immune digital pathological diagnosis analysis system, which comprises the following steps: acquiring high-resolution digital images of an immunohistochemical or immunofluorescence slice and a slide, and analyzing multicolor signal distribution in the images to obtain a quantum chromatographic image set; pixel-level color separation and intensity quantization are carried out on the quantum chromatographic image set, and a quantum intensity index set of each pixel is generated; performing multi-target color overlay analysis and post-translational modification protein specificity evaluation on the quantum intensity index set to construct a multi-color modification index set; identifying a single cell boundary and a multi-cell community based on the multicolor modification index set, and extracting a cell morphological parameter and a spatial adjacency relation to obtain a cell quantum analysis set; performing consistency correction and traceable recording by applying an automatic quality control mechanism, and generating a digital diagnosis report; the accuracy of accurate qualitative and quantitative analysis of immunohistochemistry and immunofluorescence is greatly improved.

The present invention includes a mutant Dnase1LS having at least about a 95% identity with a nucleic acid sequence encoding the protein of SEQ ID NO: 2-8 for a mutant Dnase1LS comprising at least one mutation for post-translational modification or attachment of a molecule to the mutant Dnase1LS to increase the serum half-life of the mutant Dnase1LS, nucleic acids encoding the same, host cells, and methods of making the mutant Dnase1LS.

UBAS is a critical El-activating enzyme in the UFMylation pathway, a post-translational modification process implicated in neurodegenerative diseases and cancers. Here, a high-throughput screening (HTS) assay was developed to identify inhibitors of UBAS from various compound libraries. Eighteen novel UBAS inhibitors were identified, belonging to several distinct chemical scaffolds with low micromolar IC50 values. These inhibitors demonstrated selectivity for UBAS over other El enzymes, including UBA1, and showed efficacy in inhibiting endogenous UFMylation in HEK293T cells. The identified inhibitors not only provided valuable tools for studying UFMylation but also represented potential therapeutic candidates for diseases associated with dysregulated UFMylation, such as Alzheimer's disease and cancer.

A processor is configured to implement a machine learning model that is trained to select transcripts in blood for distinguishing neurodegenerative diseases. The algorithm is developed via machine learning and leverages concepts associated with blood-based changes in mRNA gene expression for differentiating patients of any neurodegenerative disease regardless of the proteins or their post-translational modifications occurring in disease.

This invention discloses a complete set of reagents for detecting the interaction between post-translational modified proteins and their ligands. The complete set of reagents of this invention consists of four reagents: A, B, C, and D. A is composed of a biomolecule named R linked to a protein named X; B contains a biomolecule named L; R and L may be the same or different and interact with each other, with a phase transition occurring after the interaction between R and L; C is a polymer formed from a C monomer, wherein the C monomer consists of a monomer named mc, a reporter group named α, and a group named Y. C Molecules obtained by linking biomolecules, with two or more mc molecules, can form polymers; D is composed of molecules named X L The modified protein and its name is Y. D It is composed of biomolecules linked together; Y C With Y D There are interactions between them. This invention achieves high enrichment of interacting proteins and ligands in phase change droplets, amplifies weak interaction signals, and makes them easy to detect.

This application relates to antibodies or combinations of antibodies or antigen¬ binding fragment(s) thereof that comprise a first binding unit that binds to a first epitope of a target protein that harbors a post-translational modification (PTM) and a second binding unit that binds to a second epitope of a target protein that does not harbor the PTM, as well as antibody fusion molecules and multispecific antibodies or antigen-binding fragments thereof that bind to same.

Provided herein are RNA editing oligonucleotides capable of effecting ADAR-mediated deamination of a target adenosine comprised in a target RNA, wherein the oligonucleotide comprises a sequence that is capable of hybridizing with a region in the target RNA comprising said target adenosine, and wherein the oligonucleotide comprises at least one conformationally restricted nucleotide (CRN) positioned at the 5' and / or at the 3' terminus of the oligonucleotide and / or internally. In particular, the target adenosine may be part of a therapeutic target codon in the MECP2 protein-coding RNA. Provided herein are RNA editing oligonucleotides capable of effecting ADAR-mediated deamination of a target adenosine in a target RNA molecule encoding a target protein, wherein the oligonucleotide comprises a sequence that is capable of hybridizing with a region in the target RNA molecule comprising said target adenosine, and wherein the target adenosine is part of a codon encoding a posttranslational modification site in the target protein. In particular, the target adenosine may be part of a ubiquitination site in the frataxin (FXN) protein. Provided herein are RNA editing oligonucleotides capable of effecting ADAR-mediated deamination of a target adenosine in a target RNA molecule encoding a target protein, wherein the oligonucleotide comprises a sequence that is capable of hybridizing with a region in the target RNA molecule comprising said target adenosine, and wherein the target adenosine is part of a start codon in the 5' untranslated region of the target RNA molecule. In particular, the target adenosine may be part of the start codon of an untranslated ORF (uORF) in the human Sodium-dependent phosphate transporter 2 protein (SLC20A2).

The invention provides an application of an HDAH inhibitor in preparation of antibiotics. According to the invention, research finds that escherichia coli has Zn < 2 + >-dependent histone deacetylase-like amide hydrolase-HDAH, and the HDAH can directly influence the enzyme activity of metabolic enzyme through acetylation modification so as to regulate and control the metabolic level of bacteria; and the transcription level of metabolism-related genes can be indirectly regulated by acting on a transcription regulation factor (such as histone-like protein HU), and the metabolism of escherichia coli is synergistically regulated from two levels of post-translational modification and transcription. The invention also finds that the vorinostat (SAHA), the trichosaliocin (TSA) and the like can be combined with the HDAH and inhibit the deacetylation activity of the HDAH, are HDAH inhibitors, and inhibit the growth and migration ability of escherichia coli after being administered to the escherichia coli.

This invention describes compositions and methods for the delivery of fully human post-translationally modified therapeutic monoclonal antibodies, or their antigen-binding fragments, that bind to C5, to human subjects for ocular indications, particularly for the treatment of AMD. The nucleotide sequence encoding the antibody is delivered via an rAAV vector that targets ocular tissue cells for transgene expression.

Compositions and methods are described for the delivery of a fully human post-translationally modified therapeutic monoclonal antibody, or an antigen binding fragment thereof, that binds to C3 or C5 to a human subject for treatment of an ocular indication, particularly AMD. Also provided are compositions and methods for the delivery hCHL1 to a human subject for treatment of an ocular indication, particularly AMD. The nucleotide sequence encoding the antibody is delivered in a rAAV vector that targets ocular tissue cells for expression of the transgene.

Provided herein are methods of analyzing post-translationally modified proteins. The methods may comprise pre-enriching proteins using lectins and / or multiplexed detection of multiple proteins and / or multiple post-translational modifications. Provided herein are also methods for determining the likelihood that a subject has a disease or condition, such as cancer.

The invention is directed to the treatment of tauopathic neurodegenerative conditions and the underlying processes thereof. Based on the discovery that Rhes acts as a negative regulator of normal tau clearance, the compositions and methods of the invention may be applied to inhibit Rhes and reduce pathogenic tau aggregation. Rhes may be disrupted by disrupting RAS2D gene expression or reducing the abundance of Rhes protein in neurons. Additionally, post-translational modifications of Rhes may be targeted, including the disruption of Rhes farnesylation by the administration of farnesyltransferase inhibitors.

The present invention relates to a method for measuring post-translational modification of proteins in a subject. The method comprises recording infrared radiation in a predetermined wave number range attenuated by an integument of the subject, wherein the integument is still attached to the subject; and comparing the attenuation of the infrared radiation to a predetermined value in order to obtain information about post-translational modification of proteins in the integument. The present invention also relates to a corresponding system and post-translationally modified integument proteins as markers for in vivo diagnosis of diseases, such as diabetes or renal insufficiency.

This invention discloses a multispectral intelligent identification system for protein post-translational modification sites, comprising: a spectral data acquisition module, which controls different spectral analysis instruments to perform parallel spectral scanning of protein samples and performs analog-to-digital conversion and formatting to obtain various raw multispectral data of proteins; an intelligent analysis module, which preprocesses and extracts features from each type of raw multispectral data of proteins to obtain various standardized spectral feature vectors; fuses each standardized spectral feature vector to obtain a multidimensional feature vector and inputs it into a pre-trained deep learning model for modification site identification, outputting a list of identification results, which includes the location of the identified protein post-translational modification sites in the protein sequence and the modification type corresponding to each protein post-translational modification site; and a result output module, which visualizes and exports the list of identification results. This invention significantly improves the accuracy and throughput of protein post-translational modification site identification.

This invention provides a method for protein functionalization involving post-translational modification in a manner that is selective, reliable, and under the possibility of benign, moderate redox, enabling the addition of reactive functional side chains. [Solution] The present invention relates to photoredox-mediated functionalization of proteins at chemical groups via radical generation and CC bond formation using specific boronate and sulfone precursor compounds. The present invention also relates to functionalized proteins that can be produced by this method, and the specific boronate and sulfone precursor compounds themselves.

The present invention provides rapid, sensitive high-throughput methods and systems for characterizing peptides or proteins using affinity-based chromatography-coupled native mass spectrometry to improve manufacturing process of biopharmaceutical products, such as identifying impurities during antibody purification, monitoring post-translational modification variants during production, or characterizing drug-to-antibody ratio of antibody-drug conjugates. The separation profiles of the peptides or proteins are generated and compared to identify or qualify the peptides or proteins, wherein the separation profile is based on differential affinity binding.

This invention provides a polyfunctional chemical conjugation molecule that has been found to be useful as a modifier for target substrates. [Solution] A polyfunctional chemical conjugation molecule is provided, comprising a localization portion, a chemical linker portion, an activator portion, a first orientation adapter that interconnects the chemical linker portion to the activator portion at one end, and optionally a second orientation adapter that interconnects the chemical linker molecule to the localization portion at a different end. The molecule provides a use for post-translational modification of a polymer that is not a natural substrate of the activator portion. Diseases or disorders may be treated or prevented by this molecule.

The invention relates to the technical field of bioengineering, in particular to an S100A4 protein for regulating and controlling immune response as well as a preparation method and application of the S100A4 protein. According to the invention, a HaloTag-S100A4 eukaryotic expression vector is constructed, fusion protein is expressed in cells, resin specificity affinity capture is utilized, protease cleavage release is carried out, and finally the high-purity S100A4 protein is obtained. The S100A4 protein prepared by the invention has excellent biological activity and structural integrity. Due to the adoption of the eukaryotic expression system, the protein can complete correct post-translational modification, the conformation of the protein is highly consistent with that of natural protein, and the protein has high activity without complex renaturation steps. Compared with commercially available prokaryotic expression or naturally extracted S100A4 protein, the protein obtained by the invention has higher purity and fewer impurities, and interference of exogenous components on experimental results is avoided.

This application relates to the field of antibody technology, and discloses a CRP immunohistochemical antibody and its application. The antibody includes a heavy chain variable region and a light chain variable region. Combinations of the heavy chain variable region and the light chain variable region include: Combination 1: the heavy chain variable region contains the amino acid sequence shown in SEQ ID NO:2, and the light chain variable region contains the amino acid sequence shown in SEQ ID NO:4; or Combination 2: the heavy chain variable region contains the amino acid sequence shown in SEQ ID NO:6, and the light chain variable region contains the amino acid sequence shown in SEQ ID NO:8. The antibody of this application achieves precise localization by recognizing tumor cell-specific CRP conformations or post-translational modification epitopes. It specifically recognizes CRP expressed by tumor cells, completely avoiding interference from serum CRP and non-specific deposition in necrotic areas, and exhibits no background staining in normal tissues.

The present invention relates to a new variant of EPO. In this study, the inventors identified a particular EPO differing from kidney-type EPO due to a different glycosylation pattern in patients with different diseases (for example idiopathic erythrocytosis, liver / kidney disorder, tumors...). This new EPO is similar to pre-term newborn EPO produced by the liver that differs from the normal EPO produced from renal interstitial cells due to different post-translational modifications (glycosylations). This new EPO shows an increased biological activity via activation of the EPO receptor (EPOR), that can explain the origin of erythrocytosis. The detection of this specific liver-like EPO could be used as a diagnostic tool to better adapt and follow the treatments of erythrocytosis patients or in other diseases associated with the overproduction of red blood cells. Thus, the invention relates to a specific EPO protein which differs from the EPO with kidney-type glycosylation pattern.

The present invention relates to novel bifunctional molecules capable of undergoing bioorthogonal reactions and inducing proximity between two proteins, methods of inducing proximity between two proteins employing said novel molecules and bioorthogonal reactions and genetic code expansion, methods of evaluating protein-protein proximity interactions employing the novel bifunctional molecules, medical uses of the novel molecules, and methods of treatment of a disease involving post-translational modifications of a protein employing the novel bifunctional molecules.

The invention discloses a method for biosynthesizing gamma-polyglutamic acid without antibiotics, which particularly comprises the following steps: knocking out an alr gene for coding alanine racemase on a chassis strain corynebacterium glutamicum genome to construct alanine auxotroph cells, transferring alr to an expression plasmid pZM1 to construct a complementary plasmid, and successfully constructing a plasmid expression system without antibiotic addition; on the basis, gamma-polyglutamic acid degrading enzyme genes pgdS and pgsBCA derived from bacillus subtilis are subjected to tandem expression, and a dual-module formed by gamma-polyglutamic acid synthetase and degrading enzyme is further subjected to metabolism regulation by screening a promoter, RBS and a protein degradation tag at three levels of transcription, translation and post-translation modification. Under the regulation and control of a PtacM-UTR2-DAS + 8 element combination, the efficient synthesis of the gamma-polyglutamic acid is realized, the yield can reach 24.2 g.L <-1 >, and the production intensity is 0.55 g.L <-1 >. H <-1 >. And a gamma-polyglutamic acid production process without antibiotic addition is successfully constructed.

The application discloses application of a PHD3 inhibitor in prevention and treatment of AIDS. Through immunological, biochemical and other multidisciplinary research means, the application analyzes the mechanism that a viral antisense protein ASP inhibits production of type I IFN to realize immune escape and establish latent infection in an HIV-1 infection process. Mechanically, after being expressed into a protein in a cell in the body, the ASP needs to undergo post-translational modification to exert its inhibiting effect, and after hydroxylation modification of a 47-position proline, the ASP can help to realize the ability of inhibiting the body immune response, and the post-translational modification depends on a host proline hydroxylase 3 (PHD3) to realize. Based on the mechanism-based research, it is found that a PHD3 inhibitor Molidustat offsets the hydroxylation of the ASP by PHD3, thereby blocking the immune evasion of HIV-1 and antagonizing infection, and showing a good development prospect of an AIDS treatment and prevention drug.

This invention relates to monoclonal antibodies or antigen-binding fragments thereof that specifically bind to human CCR8 and are antagonists of the CCL1-CCR8 signaling pathway, particularly wherein the antibody or antigen-binding fragment specifically binds to human CCR8 regardless of the presence or absence of post-translational modifications (such as sulfated tyrosine residues at positions 15, 16, and / or 17 of human CCR8). The invention also relates to antibodies or antigen-binding fragments for therapeutic purposes, particularly for the treatment of cancer.

The invention provides a proteome tandem mass spectrum quality evaluation method based on a machine learning self-attention model encoder, which is used for evaluating the quality of proteome mass spectrum experimental data. The method can be used for identifying high-quality mass spectra (such as search parameters which are not optimized, unspecified post-translational modifications and incomplete sequence databases) which are not identified due to data analysis reasons, can also be used for evaluating the overall data quality of one experiment, provides an overall statistical overview of the proteome mass spectrum experiment data quality, and can be used for analyzing the mass spectrum of the proteome. The method is used for constructing a proteome standard data set with consistent data quality and the like, and the reliability and reproducibility of proteomics analysis conclusions are promoted.

The invention provides a protein post-translation modification data analysis processing system and method and a server, and relates to the field of protein post-translation modification data processing, the system comprises a quantitative quality control analysis module, a difference analysis module, an annotation analysis module, an enrichment analysis module, a modification site analysis module and a result summarization module which are mutually independent; wherein the quantitative quality control analysis module, the difference analysis module, the annotation analysis module, the enrichment analysis module and the modification site analysis module are respectively connected with the result summarization module; the scheme provides a modularized and automatic analysis process system compatible with various post-translation modification types, has high modularization, strong compatibility and rapid expansion capability, can realize data analysis one-key operation and automatic result output of various protein post-translation modification types, can significantly improve the development efficiency of the PTMs analysis process, and has a wide application prospect. And independent and unified management of the multi-modification data flow is realized.

The invention discloses a phage cyclopeptide library with a biphenyl-thiazole linker bond and a screening method, and relates to a polypeptide cyclization method and a strategy for discovering a protein high-affinity cyclopeptide ligand. The preparation method comprises the following steps: firstly, reacting synthesized new alkene sulfide molecules with linear polypeptide of which the nitrogen terminal and the chain are cysteine to synthesize cyclic peptide; based on the rigid biphenyl structure of the molecule in structure and the high biocompatibility of the reaction, a phage cyclopeptide library of a biphenyl-thiazoline connecting bond is obtained through a post-translational modification reaction, a high-affinity cyclopeptide ligand is screened out for target protein, and more possibilities are provided for the discovery and development of cyclopeptide compounds in drugs.

The invention discloses application of an FMR1 inhibitor in preparation of a medicine for treating immunological rejection type gastric cancer. Experimental studies prove that FTO is continuously and highly expressed in immunological rejection phenotypes and is related to interstitial activation and T cell rejection. Continuous immunohistochemistry and multiple immunofluorescence show that the FMR1 protein is highly expressed in an immunological rejection type tumor microenvironment, and most CD8 + T cells are located in tumor interstitial substances. In mechanism, the FMR1 regulates and stabilizes FTO protein and limits the degradation of proteasome of the FTO protein through post-translation, so that FTO-dependent m6A reprogramming is maintained, and an immunological rejection microenvironment is enhanced. Therefore, the invention discloses a non-classical mechanism that the FMR1 modifies and stabilizes the FTO protein after translation, and the FMR1-FTO axis can be used as a potential intervention target for breaking an immune barrier and sensitizing gastric cancer immunotherapy.

UBAS is a critical El-activating enzyme in the UFMylation pathway, a post-translational modification process implicated in neurodegenerative diseases and cancers. Here, a high-throughput screening (HTS) assay was developed to identify inhibitors of UBAS from various compound libraries. Eighteen novel UBAS inhibitors were identified, belonging to several distinct chemical scaffolds with low micromolar IC50 values. These inhibitors demonstrated selectivity for UBAS over other El enzymes, including UBA1, and showed efficacy in inhibiting endogenous UFMylation in HEK293T cells. The identified inhibitors not only provided valuable tools for studying UFMylation but also represented potential therapeutic candidates for diseases associated with dysregulated UFMylation, such as Alzheimer's disease and cancer.

The invention discloses a characterization method for post-translational modification of a GLP-1 drug containing an Fc fragment, belongs to the field of biological medicines, and is used for separating post-translational modification variants of drugs such as dulatide and Esupaglutide alpha. The method relates to reversed-phase liquid chromatography-tandem mass spectrometry in which a certain proportion of difluoroacetic acid is added into a mobile phase, and key quality evaluation indexes or identification indexes comprise 62181 Da (-380 Da) (corresponding to DesHGEG shearing) in a mass spectrum of a back peak 1 of dulatide, 59464 Da (-3125 Da) in a mass spectrum of a front peak 1 of Esupaglutide alpha, 58012 Da (-4577 Da) in a mass spectrum of a front peak 2 of Esupaglutide alpha, and the like, wherein the 52181 Da (-380 Da) and the 58012 Da (-4577 Da) respectively correspond to K28 / K46 truncation. The method has the advantages of high sensitivity, high resolution, wide applicability and the like, and enables the previous unanalyzed dulatide and Esupaglutide alpha post-translational modification to be clearly characterized.