Identification of specific small molecule ligands for stem loop 3 ribonucleic acid of the packaging signal Ψ of human immunodeficiency virus-1

Douglas Warui, Anne M. Baranger

Research output: Contribution to journalArticle

22 Scopus citations


We have screened the NCI diversity set library for molecules that bind specifically to stem loop 3 (SL3) RNA of the packaging element Ψ of HIV-1 using the docking programs DOCK and AutoDock, followed by MD simulations. The association of the predicted ligands with SL3 RNA was characterized using fluorescence, ITC, UV-melting, CD, and footprinting techniques. Nine ligands for SL3 RNA have been identified, four of which bind with higher affinity to SL3 RNA than to either single- or double-stranded RNA motifs. The most selective ligands, 9 (NSC252359) and 5 (NSC123111), bind SL3 RNA with dissociation constants of 11 μM and 98 μM, respectively. Compound 9 binds with 4-7-fold higher affinity to SL3 RNA than to the other tetraloops found in Ψ-RNA, SL2 and SL4 RNAs. The results suggest that both 9 and 5 bind to the stem region of SL3 RNA without large distortions of the SL3 RNA.

Original languageEnglish (US)
Pages (from-to)5462-5473
Number of pages12
JournalJournal of Medicinal Chemistry
Issue number17
StatePublished - Sep 10 2009


All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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