Abstract
A series of hydrophobic, water soluble and non-toxic amino acid phosphoramidate monoesters of dideoxyadenosine (ddA) and 3′-azido-3′-deoxythymidine were shown to inhibit the replication of HIV-1 in human peripheral blood mononuclear cells (PBMC) from two donors. The tryptophan methyl ester phosphoramidates of AZT and ddA were equally potent (EC50S=0.3-0.4 μM), while the phenyl methyl ester of ddA was 40- to 100- fold more potent than the AZT derivatives. The alaninyl methyl ester of AZT was found to be 70- fold more potent than the ddA derivative. The methyl amide derivatives were found to be 5-20 fold less active than the methyl esters for the ddA series, while for AZT the derivatives were found to be of similar potency or 60- to 166- fold more potent than the methylesters.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1571-1582 |
| Number of pages | 12 |
| Journal | Nucleosides, Nucleotides and Nucleic Acids |
| Volume | 20 |
| Issue number | 8 |
| DOIs | |
| State | Published - 2001 |
Bibliographical note
Funding Information:Partial financial support is gratefully acknowledged from Advanced Magnetics, Inc., and the University of Minnesota Graduate School. We also wish to thank Dr. Jean-Louis Imbach for his kind gift of ddA.
