Design and evaluation of 5′-modified nucleoside analogs as prodrugs for an E. coli purine nucleoside phosphorylase mutant
Design and evaluation of 5′-modified nucleoside analogs as prodrugs for an E. coli purine nucleoside phosphorylase mutant
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DOI：
10.1081/ncn-200059807
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发表时间：
2005-01-01
影响因子：
1.3
通讯作者：
Secrist, JA
中科院分区：
文献类型：
--
作者：
Parker, WB;Allan, PW;Secrist, JA
Our studies have led to the identification of an E. coli PNP mutant (M64 V) that is able to cleave numerous 5'-modified nucleoside analogs with much greater efficiency than the wild-type enzyme. The biological activity of the three best substrates of this mutant (9-[6-deoxy-alpha-L-talofuranosyl]-6-methylpurine (methyl(talo)-MeP-R), 9-[6-deoxy-alpha-L-talofuranosyl]-2-F-adenine, and 9-[alpha-L-lyxofuranosyl]-2-F-adenine) were evaluated so that we can optimally utilize these compounds. Our results indicated that the mechanism of toxicity of methyl(talo)-MeP-R to mice was due to its cleavage to MeP by a bacterial enzyme, and that the toxicity of the two F-Ade analogs was due to their cleavage to F-Ade by mammalian methylthioadenosine phosphorylase.
