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re- acyclic nucleotides

Jun 6, 2002

That you for your response.I have another question though?Since this is an adenosine analogue (the nucleotide that is most responsible for atp thus energizing the bodies cells)won't this cause the body to create mutated dna and mesh with body functions? Or does this drug hhave the ability to selectively only enter cd4 infected cells ? I'm really concerned about long term consequences of nukes,but realize it's impossible to create a plan without them.So I guess hiv needs things that normal cells need to replicate?Finally is adenosine the most important nucleotide from a healthy functioning cell replication standpoint?

Response from Dr. Young

Thanks for your astute questions.

Adenine is one of the nucleoside bases that is important in a number of cell functions. Yes, HIV does utilize the very same naturally-occuring nucleotides that our body needs (like adenosine triphosphate-ATP).

What makes all of the nucleotide analogues work is the specificity that they have for the HIV reverse transcriptase over other human cellular enzymes (this ratio is the therapeutic index). For some compounds that might inhibit HIV, this ratio is low-- meaning that the potential drug inhibits both the virus and the host cell; hence, they cannot be used as a viable drug. For other, more sucessful compounds, the ratio is high, meaning that the drug selectively inhibits HIV more than you or me. Some more toxic medications, like ddC, for example have a lower ratio-- inhibiting one of our cellular DNA polymerases in the same range of drug concentrations that inhibits the HIV DNA polymerase (namely reverse transcriptase). BY

thank you ! thank you!!! (Mitochondrial toxicity)

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