Synthesis and evaluation of 9-deazaguanine derivatives as multi-substrate analogue inhibitors of PNP.
9-(5',5'-Difluoro-5'-phosphonopentyl)-9-deazaguanine (DFPP-DG) and its related analogues were designed as multi-substrate analogue inhibitors against 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 P(i) concentration (about 1 mM phosphate).
Hashimoto
Mariko
M
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachiouji, Tokyo 192-0392, Japan.
Hikishima
Sadao
S
Magnowska
Lucyna
L
Bzowska
Angieszka
A
Yokomatsu
Tsutomu
T
D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*
C528379:9-(5',5'-difluoro-5'-phosphonopentyl)-9-deazaguanine; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D006147:Guanine; D011683:Purine-Nucleoside Phosphorylase