RELATIONSHIP BETWEEN CONFORMATION AND ANTIVIRAL ACTIVITY .3. 3'-AZIDOTHYMIDINE (AZT) AND 3'-AZIDO-2',3'-DIDEOXY-5-HYDROXYMETHYLURIDINE

Authors
GUPTA SV KUMAR SVP STUART AL SHI R BROWN KC ZOGHAIB WM LI J DELBAERE LTJ
Citation
Sv. Gupta et al., RELATIONSHIP BETWEEN CONFORMATION AND ANTIVIRAL ACTIVITY .3. 3'-AZIDOTHYMIDINE (AZT) AND 3'-AZIDO-2',3'-DIDEOXY-5-HYDROXYMETHYLURIDINE, Nucleosides & nucleotides, 14(8), 1995, pp. 1675-1691
Citations number
34
Categorie Soggetti
Biology
Journal title
Nucleosides & nucleotides → ACNP
ISSN journal
07328311
Volume
14
Issue
8
Year of publication
1995
Pages
1675 - 1691
Database
ISI
SICI code
0732-8311(1995)14:8<1675:RBCAAA>2.0.ZU;2-P
Abstract
3'-Azido-2',3'-dideoxy-5-hydroxymethyluridine (AZHMddUrd) was synthesi zed to improve the potency of 5-hydroxymethyl-2'-deoxyuridine (HMdUrd) against human immunodeficiency virus (HIV). AZHMddUrd was a very poor inhibitor of HIV replication (ED(50) > 200 mu M) and was also nontoxi c up to 400 mu M (highest concentration tested) to HT4-6C (HeLa CD4) c ells. AZT was phosphorylated by human cellular thymidine kinase. In co ntrast, AZHMddUrd and HMdUrd were poor substrates for the kinase. The relationship between molecular conformation and antiretroviral activit y for 3'-azidothymidine (AZT), HMdUrd and AZHMddUrd is discussed.