2′,5′-Bis-O-(terf-butyldimethylsilyl)-3′-spiro-5″- (4″-amino-1″,2″-oxathiole-2″,2″-dioxide)pyrimidine (TSAO) nucleoside analogues: Highly selective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase

Jan Balzarini, María Jesús Pérez-Pérez, Ana San-Félix, Dominique Schols, Carlo Federico Perno, Anne Mieke Vandamme, María José Camarasa, Erik De Clercq

Research output: Contribution to journalArticle

Abstract

A series of pyrimidine nucleoside analogues containing [2′,5′-bis-O-(tert-butyldimethylsilyl)-3′-spiro-5″- (4″-amino-1″,2″-oxathiole-2″,2″-dioxide)]-β- D-ribofuranose as the pentose were found to inhibit human immunodeficiency virus type 1 [HIV-1(IIIB)] replication at a concentration of 0.06-0.8 μM but were not cytotoxic at a 1000- to 10,000-fold higher concentration. These nucleoside derivatives were also effective against various other HIV-1 strains, including those resistant to 3′-azido-3′-deoxythymidine, but not against HIV-2, simian immunodeficiency virus, Moloney murine sarcoma virus, or other RNA or DNA viruses. They proved to be highly specific inhibitors of the RNA-dependent DNA polymerase function of the HIV-1 reverse transcriptase, showing no marked inhibition of the HIV-1 reverse transcriptase-associated DNA-dependent DNA polymerase activity, HIV-2 reverse transcriptase, DNA polymerase a, herpes simplex virus 1 DNA polymerase, or Thermus aquaticus DNA polymerase.

Original languageEnglish
Pages (from-to)4392-4396
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number10
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Genetics
  • General

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