title: KNI-272, a highly selective and potent peptidic HIV protease inhibitor.
abstract: Kynostatin [KNI-272; systematic name: 3-[3-benzyl-2-hydroxy-9-(isoquinolin-5-yloxy)-6-methylsulfanylmethyl-5,8-dioxo-4,7-diazanonanoyl]-N-tert-butyl-1,3-thiazolane-4-carboxamide], a highly selective and potent HIV protease inhibitor containing allophenylnorstatin [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid], has been crystallized as the hydrate, C(33)H(41)N(5)O(6)S(2) x 0.803H(2)O, from aqueous hexylene glycol. The observed disorder of the phenyl group in the structure is related to the mode of hydration. The backbone conformation of the molecule is twisted and the overall conformation of the free inhibitor is similar to that observed in its complex with HIV protease.
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan. doit@gly.oups.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Doi
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.forename: Y
authors.initials: Y
authors.lastname: Katsuya
authors.forename: M
authors.initials: M
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Mimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D011480:Protease Inhibitors; C077822:kynostatin 272