title: The rational design of inhibitors of nitric oxide formation by inducible nitric oxide synthase.
abstract: A series of compounds was rationally designed as inhibitors of dimer formation of the inducible isoform of nitric oxide synthase, and subsequent nitric oxide production. The conformation of two fragments obtained from a crystal structure was utilized to design a tether connecting those same two fragments. The resulting compounds were potent dimerization inhibitors that bound to the enzyme in a similar conformation as the fragments.
authors.affiliation: Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Whitlow
authors.forename: Marc
authors.initials: M
authors.lastname: Adler
authors.forename: David
authors.initials: D
authors.lastname: Davey
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Huang
authors.forename: Sunil
authors.initials: S
authors.lastname: Koovakkat
authors.forename: John F
authors.initials: JF
authors.lastname: Parkinson
authors.forename: Eric
authors.initials: E
authors.lastname: Pham
authors.forename: Mark
authors.initials: M
authors.lastname: Polokoff
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Shendong
authors.initials: S
authors.lastname: Yuan
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D052247:Nitric Oxide Synthase Type II