title: Design and synthesis of 6-(6-D-ribitylamino-2,4-dihydroxypyrimidin-5-yl)-1-hexyl phosphonic acid, a potent inhibitor of lumazine synthase.
abstract: A novel inhibitor of lumazine synthase, the penultimate enzyme in the biosynthesis of riboflavin, has been synthesized. The inhibitor was designed by computer graphics molecular modeling using a hypothetical structure of the enzyme-inhibitor complex. The new compound is relatively potent when compared with the known inhibitors, and displays a KI of 109 microM.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cushman
authors.forename: J T
authors.initials: JT
authors.lastname: Mihalic
authors.forename: K
authors.initials: K
authors.lastname: Kis
authors.forename: A
authors.initials: A
authors.lastname: Bacher
mesh_terms: D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology; D001665:Binding Sites; D002213:Capsid / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012258:Riboflavin Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012984:Software; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology