METHODS AND PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OF DISEASES ASSOCIATED WITH TUBULIN CARBOXYPEPTIDASES (TCP) Russian patent published in 2024 - IPC C12Q1/37 A61P25/28 

FIELD: chemistry.

SUBSTANCE: invention relates to a method of screening candidate inhibitors of the vasohibin/SVBP complex (also referred to as tubulin carboxypeptidase inhibitors — "TCP inhibitors"). The method includes the following stages: (I) incubating the candidate compound with vasohibin/SVBP (TCP) and a biotinylated peptide with the sequence Biotinyl-V-D-S-V-E-G-E-G-E-E-E-D-E-E-Y (SEQ ID NO: 13); (II) quantification, by mass spectrometry, of the biotinylated peptide Biotinyl-V-D-S-V-E-G-E-G-E-E-E-D-E-E-Y (SEQ ID NO: 13) and/or biotinylated peptide Biotinyl-V-D-S-V-E-G-E-G-E-E-E-D-E-E (SEQ ID NO: 12) present in the mixture obtained after the end of stage (I); and (III) determining whether the candidate compound is a TCP inhibitor based on the results obtained in step (II). Since the peptide according to SEQ ID NO: 13 is a TCP substrate and a tubulin tyrosine ligase (TTL) reaction product, then if the candidate compound is a TCP inhibitor, the amount of this peptide quantified in step (II) is substantially the same as and the amount of peptide initially incubated in step (I). Peptide according to SEQ ID NO: 12 is a TTL substrate and reaction product with TCP. Thus, if the candidate compound is not a TCP inhibitor, the amount of this peptide increases during step (I).

EFFECT: method according to the invention makes it possible to quickly and accurately determine TCP inhibitors.

2 cl, 19 dwg, 2 tbl, 7 ex