9-Deazaguanine derivatives: synthesis and inhibitory properties as multi-substrate analogue inhibitors of mammalian PNPs.
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.
Yatsu
Tomoyuki
T
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachiouji, Tokyo 192-0392, Japan.
Hashimoto
Mariko
M
Hikishima
Sadao
S
Magnowska
Lucyna
L
Bzowska
Agnieszka
A
Yokomatsu
Tsutomu
T
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*
C528379:9-(5',5'-difluoro-5'-phosphonopentyl)-9-deazaguanine; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D006147:Guanine; D011683:Purine-Nucleoside Phosphorylase