669results about "Detection of post translational modifications" patented technology

The invention provides methods and compositions for simultaneously detecting the activation state of a plurality of proteins in single cells using flow cytometry. The invention further provides methods and compositions of screening for bioactive agents capable of coordinately modulating the activity of a plurality of proteins in single cells. The methods and compositions can be used to determine the protein activation profile of a cell for predicting or diagnosing a disease state, and for monitoring treatment of a disease state.

This invention relates, in part, to methods and products for the detection of cancer, such as prostate cancer or multiple myeloma. This invention also relates, in part, to methods and products for the detection of prostate disease, such as benign prostatic hyperplasia (BPH). This invention further relates, in part, to methods and products for the detection of specific glycans in one or more samples, such as, for example, methods whereby specific glycans are detected and their amounts analyzed. Such methods can be used to determine relative ratios and/or threshold values for the specific glycans described herein. The relative ratios and/or threshold values can be used in the methods provided.

Disclosed are compositions and methods for modulating hemichannel function in a cell, tissue or organ. The invention also relates to useful screens for detecting such compounds, particularly those capable of modulating connexin phosphorylation. Further provided are therapeutic methods for preventing or treating conditions impacted by undesired hemichannel function in a mammal such as heart arrhythmia.

The invention provides a method detecting and quantifying proteins by mass spectrophotometric analysis using peptide internal standards and provides a highly sensitive way of detecting protein modifications. In one aspect, the invention provides a method for determining a site of ubiquitination in a polypeptide and for evaluating ubiquitination targets in a population of polypeptides. In this way, a proteome ubiquitination map can be obtained which comprises information relating to the ubiquitination states of a plurality of cellular polypeptides. Maps can be obtained for a variety of different types of cells and cell states. For example, ubiquitination targets in normal and diseased cells can be evaluated. Preferably, the map is stored as data files in a database. Individual ubiquitinated polypeptides identified can be used to generate molecular probes diagnostic of a cell state and/or can serve as targets for agents that modulate one or more cellular processes.

The instant invention provides a method for establishing safety profiles for chemical compounds, as well as pharmacological profiling said method comprising (A) testing the effects of said chemical compounds on the amount and/or post-translational modifications of two or more macromolecules in intact cells; (B) constructing a pharmacological profile based on the results of said tests; and (C) comparing said profile to the profile(s) of drugs with established safety characteristics. Additionally, the invention is also directed to a composition comprising an assay panel, said panel comprising at least one high-content assay for the amount and/or post-translational modification of a protein and at least one high-content assay for the amount and/or subcellular location of a protein-protein interaction.

The present invention provides methods for rapid deglycosylation of glycoproteins.

Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are substrate-competitive inhibitors and have an amino acid sequence designed so as to bind to a defined binding site subunit in GSK-3. Also disclosed are GSK-3 substrate competitive inhibitors which bind to the defined binding site subunit in the enzyme. Also disclosed are mutants of GSK-3 and uses thereof for identifying a putative GSK-3 substrate competitive inhibitor.

Methods for the large scale identification of post-translational modification states of proteins and enzyme activities for carrying out post-translational modification reactions involve the analysis of functional extracts from fresh and frozen samples using protein arrays. The methods and kits of the present invention can be used to analyze and characterize compounds for their effects on post-translational modifications and their pathways. The methods and kits can also be used to diagnose and characterize a wide variety of diseases and medical conditions, including cancer, neurodegenerative diseases, immune diseases, infectious diseases, genetic diseases, metabolic conditions, and drug effects using cells or body fluids of a patient.

The invention discloses 726 novel phosphorylation sites identified in carcinoma and leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies that specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.

The invention relates to a method for detecting the binding of an antibody to an Fc receptor present on the surface of a cell as well as to a method for determining the level of glycosylation of an antibody. The invention also relates to a reagent kit for carrying out these methods.

Described herein are biosensor microarrays comprising detector polypeptide monolayers substantially free of contaminants. Also provided are methods for generation of such biosensor microarrays by capture of polypeptides by arrays comprising capture moieties and associated sensors.

In sporadic Alzheimer's disease, neurofibrillary lesion formation is preceded by extensive post-translational modification of the microtubule associated protein tau. Immunoassays have been developed recently that detect tau in biological specimens, thus providing a means for pre-mortem diagnosis of Alzheimer's disease, which has remained elusive. These assays have been improved by the analysis of relevant post-translational modifications, such as phosphorylation, however opportunity for improvement remains. The present invention addresses this issue by disclosing synthetic methylated peptides derived from the tau protein of paired helical filaments and non-diseased control brain. Alzheimer's disease specificity is provided by the presence or absence of methyl moieties on lysine residues and differences between mono-, di-, and tri-methylation. The methylated peptide is useful as an antigen and a binding partner for identifying compounds that interact with the peptide and the methylated tau protein, including antibodies that can distinguish non-diseased brain from that affected by Alzheimer's disease. The resulting antibodies are useful diagnostically and therapeutically. The compounds that specifically bind to methylated tau proteins are useful for eliminating abnormally methylated tau.

This invention discloses “Artificially Cleaved Epitope (ACE)” methods, antibodies, reagents, immunoassays, and kits for designing and detecting hidden epitopes/antigens. The ACE methods can detect epitopes that are either absent or poorly accessible naturally to antibodies, and thus must be specifically and artificially created (free terminals) and/or exposed in samples and sample preparations for antibody detection. The ACE structures include, but are not limited to, macromolecule-to-macromolecule conjugation sites, and any types of linear hidden epitopes. The ACE methods comprise ACE antigen design and ACE antigen detection. The ACE methods, antibodies, reagents, immunoassays, and kits are useful in research and discovery, diagnostic, and therapeutic applications. In another aspect, the ACE methods can artificially and specifically expose hidden antigens while reducing the antibody non-specific bindings in all antibody-based applications.

The invention is based on the surprising discovery that as few as one episode of blast exposure increases the risk of CTE. Blast exposure is associated with chronic traumatic encephalopathy, impaired neuronal function, and persistent cognitive deficits in blast-exposed military veterans and experimental animals. Early diagnosis and assessment of risk permits physicians to prescribe treatment to reduce or slow progression of impairment before the onset of overt symptoms that become apparent decades after an initial insult or trauma to brain tissue. The invention provides methods and compositions for diagnosis and prognosis of individuals at risk of long term complications related to blast injury or concussive injury.

Disclosed are methods for diagnosing and prognosing Inflammatory Bowel disease or Crohn's disease (CD) by measuring levels of antibodies to glycans in a biological sample.

A cartridge for measuring a concentration of a glycated protein in a wide measurement range, a system for measuring a glycated protein, and a method of measuring a glycated protein using same.

Described herein are devices and methods for extracting cellular material from living cells and then depositing them into to a receptacle in a nanoliter scale. Using a nanopipette integrated into a scanning ion conductance microscope (SICM), extraction of mitochondrial DNA from human BJ fibroblasts and Green Fluorescent Protein (GFP) transcripts from HeLa/GFP cells was achieved with minimal disruption to the cellular milieu and without chemical treatment prior to obtaining the isolated sample. Success of the extraction was confirmed by fluorescence microscopy and PCR analysis of the extracted material. The method and apparatus may be applied to many different cell types and intracellular targets, allowing not only single cell analysis, but single subcellular compartment analysis of materials extracted in their native state.