98 results about "Posttranslational modification" patented technology

This disclosure provides nanoparticle compositions, and use thereof for isolating and measuring proteins, protein degrader action, and cells. The disclosed nanoparticles can be identified by barcodes that reveal the identity of and post translational modifications to the bound protein using image processing techniques described herein.

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 invention discloses a multispectral intelligent identification system for protein post-translational modification sites, comprising: a spectral data acquisition module for controlling different spectrum analyzers to perform spectrum scanning and analog-to-digital conversion and formatting on protein samples in parallel to obtain multiple protein multispectral original data; the intelligent analysis module is used for carrying out preprocessing and feature extraction on the multi-spectral original data of each protein to obtain a plurality of standardized spectral feature vectors; fusing each standardized spectral feature vector to obtain a multi-dimensional feature vector, inputting the multi-dimensional feature vector into a pre-trained modification site recognition deep learning model, and outputting a recognition result list, the recognition result list comprises the positions of the recognized protein post-translation modification sites in the protein sequence and modification types corresponding to the protein post-translation modification sites; and the result output module is used for visually displaying and exporting the identification result list. According to the method, the accuracy and flux of protein post-translational modification site recognition are remarkably 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.

The invention discloses a green algae expression method and application of recombinant human serum albumin, and belongs to the technical field of biology. Aiming at the problems of high cost and incomplete post-translational modification of the existing recombinant protein expression system, the invention provides a technical scheme for efficiently expressing human serum albumin by using green algae. The method comprises the following steps: carrying out codon optimization on a human serum albumin gene sequence, introducing a recombinant vector into green algae cells, and screening transgenic algae strains through a culture medium containing a resistance agent, culturing the transgenic algal strain, splitting the algal cells and separating the recombinant albumin. According to the method, efficient production of the human serum albumin is achieved through a green alga expression system, and the product has a correct folding structure and biological activity and is mainly used for preparing medical plasma substitutes, drug carriers and biological agents.

The invention discloses a method for detecting polypeptide sequence difference and post-translational modification thereof based on a nanopore system, the nanopore system is constructed in the method, and the nanopore system comprises an alpha-hemolysin nanopore and octa-amino modified gamma-cyclodextrin embedded in the nanopore; the amino acid sequence of the alpha-hemolysin nanopore comprises mutation sites M113R and T145R, and the alpha-hemolysin nanopore is characterized in that the alpha-hemolysin nanopore According to the detection method, polypeptide with negative charges enters a nanopore under the driving of external voltage, an ion current blocking signal is recorded, and the polypeptide sequence difference and post-translational modification are analyzed according to blocking amplitude, duration, noise characteristics and event frequency. The method can detect a peptide chain with the length of 2-10 amino acid residues, can distinguish the post-translational modification state in homopolypeptide composed of 4-10 amino acids and polypeptide by single amino acid resolution, and can be used for protein enzyme digestion product analysis, oligopeptide drug detection and rapid polypeptide identification under the condition of no mass spectrum.

The invention discloses a preparation method and application of high-activity recombinant collagen, and relates to the field of biological medicine, and the preparation method comprises the following steps: S1, providing engineering bacteria containing a recombinant collagen expression vector, and performing seed culture; s2, inoculating the seed solution into a fermentation culture medium for fermentation culture; s3, in the fermentation process, when the thallus density reaches a preset value, a signal factor without an animal source is added into a fermentation system, and the signal factor is bionic polypeptide; s4, after the signal factors are added, the fermentation conditions are adjusted, and target collagen expression is induced; according to the preparation method and the application of the high-activity recombinant collagen, an endogenous metabolic network of bacteria is actively regulated and controlled by accurately adding animal-source-free bionic polypeptide signal factors in the fermentation process of engineering bacteria, and correct folding and specific post-translational modification of target collagen are induced; therefore, the hydroxylation rate and the biological activity of the recombinant collagen are improved, and the structure and the function of the recombinant collagen are closer to those of natural collagen of a human body.

The invention relates to a recombinant hirudin fusion protein, a coding gene and a prokaryotic expression method and application of the recombinant hirudin fusion protein. The recombinant hirudin fusion protein comprises an HMg variant amino acid sequence and a fusion tag. The recombinant hirudin fusion protein has the advantages that the hirudin variant in poecilobdella manillensis is adopted to construct an efficient prokaryotic expression system, the hirudin yield and activity are improved under the condition that post-translational modification is not needed, the anticoagulant efficiency and the production process of the recombinant hirudin fusion protein provide an important basis for development of a new generation of antithrombotic drugs, and the recombinant hirudin fusion protein has wide application prospects. The progress of cardiovascular disease treatment and hirudin production is expected to be promoted.

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.

Compositions and methods are described for the delivery of a fully human post-translationally modified (HuPTM) monoclonal antibody (“mAb”) or the antigen-binding fragment of a mAb against human vascular endothelial growth factor (“hVEGF”)—such as, e.g., a fully human-glycosylated (HuGly) anti-hVEGF antigen-binding fragment—to the retina / vitreal humour in the eye(s) of human subjects diagnosed with ocular diseases caused by increased neovascularization, for example, neovascular age-related macular degeneration (“nAMD”), also known as “wet” age-related macular degeneration (“WAMD”), age-related macular degeneration (“AMD”), and diabetic retinopathy.

The invention provides a proteomics complex post-translational modification large-scale rapid identification method which comprises the following steps: preprocessing original protein data of a sample to obtain a primary signal peak cluster and a candidate secondary signal peak set corresponding to each primary signal peak; determining a first-level signal peak and a second-level signal peak pair based on the first-level signal peak cluster and the candidate second-level signal peak set; based on a pre-trained deep learning model and the peak pair of the first-level signal peak and the second-level signal peak, obtaining a matching score of the peak pair of the first-level signal peak and the second-level signal peak; and constructing a target pseudo secondary spectrogram based on the matching score, and performing open search on the target pseudo secondary spectrogram to obtain an identification result containing post-translation modification. According to the method, deconvolution can be carried out on the complex secondary spectrogram under methods including independent collection, the target pseudo secondary spectrogram which can be directly used for open type search is generated, and then accurate identification and deep analysis of accidental modification signals are achieved.

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.

Compositions and methods are described for the delivery of a fully human post-translationally modified therapeutic monoclonal antibody that binds to plasma kallekrein (pKal) to a human subject diagnosed with a disease or condition indicated for treatment with an anti-pKal antibody. Compositions and methods are also described with liver specific promoter combinations to enhance gene expression in liver cells. Such diseases include hereditary angioedema, as well as ocular indications, such as diabetic retinopathy and diabetic macular edema. Dosing of viral vectors encoding the anti-pKal antibody to achieve therapeutically effective serum levels is provided.

The invention relates to the technical field of biology, in particular to acoustoelectric Ba0. 85Ca0. 15Ti0. 9Yb0. 1O3 nanoparticles capable of triggering post-translational modification as well as a preparation method and application of the acoustoelectric Ba0. 85Ca0. 15Ti0. 9Yb0.1 O3 nanoparticles. Stirring and mixing the titanium tetrachloride solution and the mixed reagent solution to obtain a stirred mixed solution; mixing the stirred mixed solution with sodium hydroxide and polyvinylpyrrolidone, and performing heat treatment to obtain a heat-treated substance; and carrying out solid-liquid separation on the heat-treated substance to obtain a solid, washing the solid to be neutral, and drying. The nanoparticles provided by the invention consume H < + > near mitochondria under ultrasonic stimulation, so that mitochondrial membrane potential depolarization is caused. After mitochondrial membrane potential depolarization, E3 ubiquitin ligase Parkin is transferred from cytoplasm to a mitochondrial outer membrane, and is massively gathered and accumulated on the mitochondrial outer membrane, so that ubiquitination modification and cascade degradation of mitochondrial outer membrane anti-apoptosis protein MCL-1 are caused, and cell apoptosis is promoted.

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.

The application discloses a protein post-translational modification prediction method based on multi-head attention, and belongs to the technical field of biological information, and comprises the following steps: preprocessing protein sequences with post-translational modification annotation information to obtain a legal character set, a second protein sequence data set and a benchmark data set; obtaining three kinds of vocabulary tables based on the legal character set; performing multi-scale division on protein sequence samples in the second protein sequence data set to obtain a single amino acid scale data set, a dipeptide scale data set and a tripeptide scale data set; training a corpus by using a Skip-gram model structure to obtain three kinds of word vector models; performing label prediction on protein sequence fragments of the benchmark data set by using a multi-head attention model to obtain protein sequence fragment prediction results; and the multi-scale word vector is used to comprehensively utilize polypeptide composition information in the original protein sequence, and the dependence on biological feature engineering is reduced.

The invention discloses an application of a PHD3 inhibitor in prevention and treatment of AIDS (acquired immune deficiency syndrome). Through multidisciplinary research means of immunology, biochemistry and the like, the situation that virus antisense protein ASP inhibits generation of I-type IFN in the HIV-1 infection process is analyzed, immune escape is achieved, and a latent infection mechanism is established. In the aspect of mechanism, the ASP can play the inhibiting role after transcriptional expression into protein in a body cell through post-translational modification, the 47-site proline of the ASP can be helped to realize the capability of inhibiting the immune response of the body after hydroxylation modification, and the post-translational modification is realized by depending on proline hydroxylase 3 (PHD3) of a host. On the basis of mechanism research, it is found that a PHD3 inhibitor Molidustat counteracts hydroxylation of PHD3 to ASP, so that immune escape of HIV-1 is blocked, infection is antagonized, and good development prospects of AIDS treatment and prevention drugs are shown.

The present disclosure provides modulators of proteasome dynamics and / or function in a mammalian cell, compositions and uses thereof. The disclosed modulating compounds are characterized by affecting at least one of: mammalian target of rapamycin (mTOR) activation and / or lysosomal association, proteasome cellular localization, the activity and / or level / s and / or the post translational modification / s (PTM / s), and / or subcellular localization of at least one signaling molecule participating directly or indirectly in at least one pathway mediating said proteasome dynamics / function.

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.