Peptidic alpha-ketocarboxylic acids and sulfonamides as inhibitors of protein tyrosine phosphatases.
One common approach for designing protein tyrosine phosphatase (PTPase) inhibitors is to incorporate a nonhydrolyzable phosphotyrosine (pTyr) mimic into a peptide substrate for PTPases. This report describes the synthesis of three such nonhydrolyzable pTyr mimics that contain alpha-ketoacid, alpha-hydroxyacid, and methylenesulfonamide functional groups in place of the phosphate. These pTyr mimics were incorporated into the peptide sequence Ac-Asp-Ala-Asp-Glu-X-Leu-NH(2), where X is the pTyr mimic, and analyzed for activity against the Yersinia PTPase and PTP1B.
Chen
Yen Ting
YT
Department of Chemistry, Brown University, 324 Brook St. Box H, Providence, Rhode Island 02912, USA.
Xie
Jian
J
Seto
Christopher T
CT
D001665:Binding Sites; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D020128:Inhibitory Concentration 50; D007651:Keto Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry; D015007:Yersinia / Q000201:enzymology*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007651:Keto Acids; D010455:Peptides; D013449:Sulfonamides; D017027:Protein Tyrosine Phosphatases