Carbocyclic 2',3'-didehydro-2',3'-dideoxyguanosine (carbovir, NSC 614846) is an 
anti-retroviral agent that may be useful in the treatment of AIDS. We have 
examined the ability of (-)-enantiomeric carbovir triphosphate to inhibit human 
immunodeficiency virus type 1 (HIV-1) reverse transcriptase (EC 2.7.7.49). A 
comparison of inhibition kinetics was made with 3'-azido-2',3'-dideoxythymidine 
triphosphate and phosphonoformate. Inhibition of the reverse transcriptase was 
evaluated using poly(rA).oligo(dT)12-18, poly(rC).oligo(dG)12-18, or influenza 
virion RNA template with a specific oligodeoxynucleotide as primer. (-)-Carbovir 
5'-triphosphate was shown to be a potent inhibitor of HIV-1 reverse 
transcriptase with an apparent Ki similar to that of 
3'-azido-2',3'-dideoxythymidine triphosphate. Chain elongation studies utilizing 
an MS2 RNA template showed that (-)-carbovir 5'-triphosphate terminated 
transcription at positions identical to those where dideoxy-GTP terminated. This 
indicates that (-)-carbovir 5'-monophosphate is incorporated into the newly 
synthesized DNA and terminates transcription at that point. We conclude that 
(-)-carbovir 5'-triphosphate is a potent inhibitor of the HIV-1 reverse 
transcriptase enzyme and that (-)-carbovir most likely inhibits HIV by activity 
at the triphosphate level by a combination of direct competition for binding of 
the natural deoxynucleoside triphosphates to the reverse transcriptase and chain 
termination.