New insights into the design of inhibitors of human S-adenosylmethionine decarboxylase: studies of adenine C8 substitution in structural analogues of S- …

…, S Bale, JA Secrist III, A Tiwari, TH Moss III…

Index: McCloskey, Diane E.; Bale, Shridhar; Secrist III, John A.; Tiwari, Anita; Moss III, Thomas H.; Valiyaveettil, Jacob; Brooks, Wesley H.; Guida, Wayne C.; Pegg, Anthony E.; Ealick, Steven E. Journal of Medicinal Chemistry, 2009 , vol. 52, # 5 p. 1388 - 1407

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Citation Number: 25

Abstract

S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution ...