Synthesis and evaluation of 9-deazaguanine derivatives as multi-substrate analogue inhibitors of PNP | Zendy

Masashi Hashimoto | Zendy; Sadao Hikishima | Zendy; Lucyna Magnowska | Zendy; Agnieszka Bzowska | Zendy; T. YOKOMATSU | Zendy

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Synthesis and evaluation of 9-deazaguanine derivatives as multi-substrate analogue inhibitors of PNP

Author(s) -

Masashi Hashimoto,

Sadao Hikishima,

Lucyna Magnowska,

Agnieszka Bzowska,

T. YOKOMATSU

Publication year - 2007

Publication title -

nucleic acids symposium series

Language(s) - English

Resource type - Journals

eISSN - 1746-8272

pISSN - 0261-3166

DOI - 10.1093/nass/nrm216

Subject(s) - purine nucleoside phosphorylase , chemistry , stereochemistry , substrate (aquarium) , guanine , purine , enzyme , nucleotide , biochemistry , biology , ecology , gene

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).

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