Phosphoglycerate mutases and enzyme products

摘要

Use of PGM (phosphoglycerate mutase), or cell lysate containing it or cytoplasmic fractions enriched in it, to screen for compounds (I) with PGM-inhibitory activity, comprising contacting the test compound, or compounds, with the PGM material and measuring PGM activity, particularly in absence and presence of test compound, is new. Independent claims are also included for: (1) use of bis-PGM (2,3-bisphosphoglycerate mutase), or cell lysates or cytosolic fractions containing it, to screen for compounds (II) that increase its activity, in an activity assay; (2) screening (M1) for compounds (III) that increase transcription or translation rate of bis-PGM; (3) peptides comprising an 8 amino acid sequence (SEQ ID NO.1) or 31 amino acid sequence (SEQ ID NO.4) both fully defined in the specification; (4) peptide of SEQ ID NO.1 attached at either end to a transport molecule; (5) nucleic acid (IV) that encodes a 6 amino acid (SEQ ID NO.3) and 31 amino acid (SEQ ID NO.4) peptide fully defined in the specification; (6) vector (V) that contains (IV); (7) cells transformed with (V); (8) quantifying (M2) protein phosphorylation activity of the Nm23-H1/GAPDH complex (X) or PGM-phosphorylating enzyme activity; (9) use of Nm23-H1 and/or GAPDH, or complex (X), to screen for compounds that: (a) compete with binding of PGM; (b) after binding, inhibit or inactivate (X) or (c) are potential detection agents; (10) quantifying (M3) (X); (11) use of bis-PGM, or its catalytically active fragment, optionally bound to a transport molecule in pharmaceutical compositions; and (12) increasing the content (M4) of 2,3-BPG (2,3-bisphosphoglycerate) in the cells of an organism. Pro-Trp-Leu-Ile-Arg-His-Gly-Glu (SEQ ID No.1) Met-Arg-Gln-Ile-Lys-Ile-Trp-Phe-Pro-Asn-Arg-Arg-Met-Lys-Trp-Lys (SEQ ID NO.2) His-His-His-His-His-His (SEQ ID NO.3) Met-Arg-Gln-Ile-Lys-Ile-Trp-Phe-Pro-Asn-Arg-Arg-Met-Lys-Trp-Lys-Lys-Lys-(His)6-Pro-Trp-Leu-Ile-Arg-His-Gly-Glu (SEQ ID No.4) ACTIVITY : Cytostatic. MECHANISM OF ACTION : Phosphoglycerate mutase inhibitor.