摘要:
The free thiol group present in free cysteines in recombinant therapeutic antibodies are reactive to process components and generates product variants during early stages of biosimilar development. Free thiol group present on the structural motifs, especially in the complementary determining regions (CDR), support maximal antigen binding capability. Product variants associated with these free thiol groups are detrimental for safety and efficacy of these therapeutic antibodies. Methods to identify and characterize various thiol variants an antibody composition is provided and an anti-IL-17A IgG1 composition having these thiol variants are described.
摘要:
The present invention relates to peptides and peptidomimetics as well as their medical use in the treatment of hyperproliferative diseases and inflammatory diseases.
摘要:
The invention pertains to a method to identify an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein, wherein the combination is effective when the transmembrane E3 ubiquitin ligase is capable of decreasing the surface level of the membrane-bound protein upon forced dimerization, preferably by ubiquitination of the membrane-bound protein. The method of the invention comprises a step of exposing a cell to a heterobifunctional molecule, wherein the heterobifunctional molecule comprises a first binding domain capable of specific binding to an extracellular portion of the transmembrane E3 ubiquitin ligase, and a second binding domain capable of specific binding to an extracellular portion of the membrane-bound protein. The method further comprises a step of determining the decrease in surface level of the membrane-bound protein. The invention additionally pertains to a heterobifunctional molecule targeting an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein.
摘要:
[Problem]To provide a mitochondria-function regulator effective for treatment or prevention of obesity, and a screening method therefore.[Solution]The mitochondria-function regulator of the present invention contains, as an active ingredient, a PGC-1β-protein function regulator synoviolin. The screening method of the present invention includes a step for causing a test substance to act on an adipose tissue cell or an individual animal, and measuring or detecting one or more of the following in the adipose tissue cell: (1) expression level of synoviolin; (2) a bond between synoviolin and PGC-1β protein; and (3) the ubiquitination of the PGC-1β protein by synoviolin.
摘要:
[Problem] To provide: a method for utilizing a novel marker, including a method for determining depression; and a kit for analyzing an ubiquitinated serotonin transporter.[Solution] A method for determining depression, comprising a step of analyzing the proportion of an ubiquitinated serotonin transporter in a blood sample collected from a subject; and a kit for analyzing an ubiquitinated serotonin transporter in blood, which comprises an ubiquitinated protein collector material and an anti-serotonin transporter antibody and is used for the analysis of the proportion of an ubiquitinated serotonin transporter in a collected blood sample.
摘要:
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.
摘要:
The present invention describes an unbiased catalytic tagging system to search for target substrates. Identification of substrates for specific baits is accomplished by utilizing an orthogonal system consisting of an E1 activating enzyme, an E2 ubiquitin-like conjugating enzyme, and baits that are fused to the E2 ubiquitin-like conjugating enzyme. The present invention thus reveals important mutually antagonistic substrates of specific baits.
摘要:
Provided herein is a novel binding pocket within NEDD8 co-E3 proteins that binds NEDD8 E2 enzymes. Particularly at its M-Terminus. Methods are provided for screening for compounds that bind to the disclosed E2-binding pocket in NEDD8 co-E3 proteins. Compounds that bind to the E2-binding pocket and optionally inhibit the activity of NEDD8 co-E3 proteins and pharmaceutical compositions comprising the same are further provided. The NEDD8 co-E3 inhibitors find use, as agents preventing the NEDDylation of a target protein, in inhibiting cell growth and methods for treating cancers, inflammatory disorders, and pathogenic infections. The preferred inhibitors are peptides corresponding to a M-terminal fragment of Dnc1, e.g. MTLASKLKRDD, MLKLRQLQKKKQ, and MIKLFSLKQQKK, which are substituted at the M-Terminus with an uncharged group (e.g. acyl).
摘要:
The invention features methods and kits for determining the presence of, or a predisposition to develop, Sjögren's syndrome in humans. The invention features methods to detect changes in the levels of one or more LMP-2 protein isoforms, in particular phosphorylated isoforms of LMP-2, and to detect changes in cellular protein phosphorylation and ubiquitination in samples from Sjögren's patients.