title: A disubstituted NAD+ analogue is a nanomolar inhibitor of trypanosomal glyceraldehyde-3-phosphate dehydrogenase.
abstract: N6-Naphthalenemethyl-2'-methoxybenzamido-beta-NAD+, a derivative of a low micromolar first-generation inhibitor of trypanosomal glyceraldehyde phosphate dehydrogenase (GAPDH), was synthesized, taking advantage of methodology for the selective phosphitylation of nucleosides. The compound was found to be a poor alternate cosubstrate for GAPDH, but an extremely potent inhibitor. Although intended for use in crystallization trials, the analogue presents possibilities for further drug design.
authors.affiliation: Department of Chemistry, University of Washington, Seattle 98195, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Kennedy
authors.forename: J C
authors.initials: JC
authors.lastname: Bressi
authors.forename: M H
authors.initials: MH
authors.lastname: Gelb
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018929:Cell Culture Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology; D009243:NAD / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014345:Trypanosoma / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D009243:NAD; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases