title: Convergent synthesis of alpha-ketoamide inhibitors of Pin1.
abstract: A convergent synthesis of alpha-ketoamide inhibitors of Pin1 is described. An alpha-hydroxyorthothioester derivative of Ser was reacted directly with an amine synthon. The reaction was catalyzed by HgO and HgCl(2) to form alpha-hydroxyamide. Thus, hydrolysis and coupling were combined in one step with 80% yield. Two diastereomers of a phospho-Ser-Pro alpha-ketoamide analogue were synthesized. The IC(50) values of 100 and 200 microM were surprisingly weak for Pin1 peptidyl prolyl isomerase.
authors.affiliation: Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, USA.
authors.forename: Guoyan G
authors.initials: GG
authors.lastname: Xu
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Etzkorn
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D007659:Ketones; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase