G01N33/6842

KDAC VARIANTS AND USES THEREOF
20200240995 · 2020-07-30 ·

The invention provides a method of selecting a mutant polypeptide having lysine demodification, in particular lysine deacylation, activity, wherein the method comprises the following steps (a) incubating a mutant polypeptide having an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 1 with a peptide or polypeptide comprising an inactivated essential lysine residue; and (b) determining the activity of the mutant polypeptide to activate the peptide or polypeptide comprising the inactivated essential lysine residue, wherein the mutant polypeptide and the peptide or polypeptide comprising an inactivated essential lysine residue are incubated in a biological cell. The invention furthermore relates to an acylated luciferase, particularly Firefly luciferase, and uses thereof. The present invention furthermore relates to a mutant polypeptide comprising an amino acid sequence having at least 98% sequence homology with SEQ ID NOs: 2, 3, 4, 5 or 6 and having lysine demodification, in particular lysine deacylation, activity, wherein the mutant polypeptide is not identical to SEQ ID NO: 1. The invention also relates to the mutant polypeptide of the invention and a peptide or polypeptide comprising an inactivated essential lysine residue for use in treating cancer.

IDENTIFICATION AND USE OF BIOLOGICAL PARAMETERS FOR DIAGNOSIS AND TREATMENT MONITORING

Systems and methods of quantifying a glycomic parameter, a genomic parameter, a proteomic parameter, a metabolic parameter, and/or a lipidomic parameter of a biological sample; obtaining a clinical parameter associated with a subject from which the one or more biological samples originated; determining one or more relationships between one or more of: (i) one or more of the quantified glycomic parameters, genomic parameters, proteomic parameters, metabolic parameters, and lipidomic parameters, (ii) a predetermined range associated with one or more of the quantified glycomic parameters, genomic parameters, proteomic parameters, metabolic parameters, and lipidomic parameters, and (iii) an obtained clinical parameter; identifying one or more biomarkers based on one or more of the determined relationships satisfying a predetermined significance criteria; and/or determining a wellness classification state of a wellness classification, the determination of the wellness classification state determined based on the one or more identified biomarkers.

Method for Selecting Agents that Bind to Transmembrane Receptors in a Conformationally Selective Manner

Provided herein are several methods for selecting agents that bind to transmembrane receptors in a conformationally-selective way. In some embodiments, the method may comprise producing: a transmembrane receptor in an active conformation; and said transmembrane receptor in an inactive conformation and using cell sorting to select, from a population of cells comprising a library of cell surface-tethered extracellular capture agents, cells that are specifically bound to either the transmembrane receptor in its active conformation or the transmembrane receptor in its inactive conformation, but not both. In other embodiments, the method may comprise: contacting a GPCR with a population of cells that comprise a library of surface-tethered extracellular proteins; labeling the cell population with a conformationally-specific binding agent, e.g., a G-protein or mimetic thereof; and using cell sorting to select from the cell population cells that bind to the agent.

Mitochondrial preproteins as markers for Alzheimer's disease

The present invention is inter alia concerned with a method of diagnosing Alzheimer's disease in a patient, wherein said method is based on determining the amount of at least one premature mitochondrial protein. Further, the present invention relates to the use of such a protein as marker for Alzheimer's disease. Accordingly, antibodies binding to such a preprotein may be used for diagnosing Alzheimer's disease. The present invention is based on the finding that premature mitochondrial proteins accumulate in Alzheimer's disease.

Method of analyzing post-translational modifications

The invention relates to a new method of determining the presence, absence, number or position(s) of one or more post-translational modifications in a peptide, polypeptide or protein. The invention uses transmembrane pores.

Chemical and biochemical adducts as biomarkers for organophosphate exposure

Provided are methods for identifying OP-adducted biomarkers of OP exposure as well as compounds containing OPs that can provide OP adducts and compounds of Formula 1 for eliciting antibodies that specifically and selectively bind to the OP adducts, wherein the Formula 1 compounds have the structure of OP-Peptide-Linker-CP, wherein CP is a carrier protein, OP represents a structure corresponding to that of a reactive organic phosphorous compound covalently modifying a tyrosine residue hydroxyl group of the peptide of Formula I and the other variable groups are as described herein.

NEUKINASE, A DOWNSTREAM PROTEIN OF NEUREGULIN
20200207870 · 2020-07-02 ·

The present invention relates to neukinase, a downstream protein kinase in the neuregulin signaling pathway. In certain aspects, the present invention provides isolated neukinase-encoding nucleic acids, neukinase polypeptides, oligonucleotides that hybridize to neukinase nucleic acids, and expression vectors containing neukinase-encoding sequences. The present invention further provides isolated host cells, antibodies, transgenic non-human animals, compositions, and kits relating to neukinase. In other aspects, the present invention further provides methods of identifying predisposition to cardiac dysfunction, methods of detecting the presence of neukinase, neukinase nucleic acid, methods of screening for agents which affect neukinase activity, and methods of modulating neukinase activity.

Methods for identifying, diagnosing, and predicting survival of lymphomas

Gene expression data provides a basis for more accurate identification and diagnosis of lymphoproliferative disorders. In addition, gene expression data can be used to develop more accurate predictors of survival. The present invention discloses methods for identifying, diagnosing, and predicting survival in a lymphoma or lymphoproliferative disorder on the basis of gene expression patterns. The invention discloses a novel microarray, the Lymph Dx microarray, for obtaining gene expression data from a lymphoma sample. The invention also discloses a variety of methods for utilizing lymphoma gene expression data to determine the identity of a particular lymphoma and to predict survival in a subject diagnosed with a particular lymphoma. This information will be useful in developing the therapeutic approach to be used with a particular subject.

Methods for enriching glycopeptides for global analysis of glycoproteins

Compositions and methods for enriching glycocompounds are disclosed which can comprise a glycocompound bound to a boronic acid compound which can be conjugated to a dendrimer.

Senescent Cell Biomarkers
20200182871 · 2020-06-11 ·

The invention relates to senescent cell biomarkers and the uses thereof. The invention also extends to methods and kits for detecting senescence, and drug conjugates and pharmaceutical compositions for killing senescent cells.