title: 9-Deazaguanine derivatives: synthesis and inhibitory properties as multi-substrate analogue inhibitors of mammalian PNPs.
abstract: 9-(5',5'-Difluoro-5'-phosphonopentyl)-9-deazaguanine (DFPP-DG) and its related analogues were designed as multi-substrate analogue inhibitors of purine nucleoside phosphorylase (PNP) on the basis of the X-ray crystallographic data obtained for the binary complex of 9-(5',5'-difluoro-5'-phosphonopentyl)guanine (DFPP-G) with calf spleen PNP. One of these analogues, homo-DFPP-DG was found to be a very potent PNP inhibitor at an intracellular (approximately 1 mM) phosphate concentration.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachiouji, Tokyo 192-0392, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yatsu
authors.forename: Mariko
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Sadao
authors.initials: S
authors.lastname: Hikishima
authors.forename: Lucyna
authors.initials: L
authors.lastname: Magnowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bzowska
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yokomatsu
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*
chemical_list: C528379:9-(5',5'-difluoro-5'-phosphonopentyl)-9-deazaguanine; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D006147:Guanine; D011683:Purine-Nucleoside Phosphorylase