The nucleoside, 3'-amino-3'-deoxythymidine, has been found to be a potent, linear, non-competitive inhibitor of human immunodeficiency virus reverse transcriptase. As a potential lead to understanding the mechanism of inhibitor of HIV reverse transcriptase by nucleotide analogs, the conformation of the nucleoside has been investigated by NMR and X-ray. In the solid state, a rare syn conformation is assumed by the glycoside; in solution, the normal anti conformation is observed. The hydrogen bonding capacity of the 3'-amino moiety relates to the unusual crystal conformation and perhaps to the unusual HIV reverse transcriptase inhibitory behavior. Poly(2'-fluoroadenylic acid), a potent inhibitor of Maloney murine leukemia virus reverse transcriptase, fails to inhibit the HIV reverse transcriptase.
