Interference with HIV-1 reverse transcriptase-catalyzed DNA chain elongation by the 5'-triphosphate of the carbocyclic analog of 2'-deoxyguanosine.
In an effort to better understand features in nucleotide analogs that result in the inhibition of HIV-1 reverse transcriptase, we have evaluated this enzyme with the 5'-triphosphate of the carbocyclic analog of 2'-deoxyguanosine (CdG-TP). CdG-TP was a reasonably potent competitive inhibitor of the incorporation of dGTP into DNA by HIV-1 reverse transcriptase using either a RNA or DNA template (Ki, 1 microM). CdG-TP was a good substrate for HIV-1 reverse transcriptase on both templates, but the DNA chain was poorly extended beyond the incorporation of CdG. These results indicate that substitution of ribose with a cyclopentane ring in nucleotides is not well tolerated by HIV-1 reverse transcriptase.
D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D004279:DNA, Viral / Q000378:metabolism*; D003848:Deoxyguanine Nucleotides / Q000378:metabolism / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D008969:Molecular Sequence Data; D018894:Reverse Transcriptase Inhibitors; D013698:Templates, Genetic
D000998:Antiviral Agents; D004279:DNA, Viral; D003848:Deoxyguanine Nucleotides; D018894:Reverse Transcriptase Inhibitors; C078627:carbocyclic 2'-deoxyguanosine 5'-triphosphate; C029603:deoxyguanosine triphosphate; D054303:HIV Reverse Transcriptase