| Literature DB >> 16247956 |
William B Parker1, Paula W Allan, Steve E Ealick, Eric J Sorscher, Abdalla E A Hassan, A V Silamkoti, Anita T Fowler, William R Waud, John A Secrist.
Abstract
Our studies have led to the identification of an E. coli PNP mutant (M64V) 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.Entities:
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Year: 2005 PMID： 16247956 DOI： 10.1081/ncn-200059807
Source DB: PubMed Journal: Nucleosides Nucleotides Nucleic Acids ISSN： 1525-7770 Impact factor: 1.381