title: Identification of specific small molecule ligands for stem loop 3 ribonucleic acid of the packaging signal Psi of human immunodeficiency virus-1.
abstract: We have screened the NCI diversity set library for molecules that bind specifically to stem loop 3 (SL3) RNA of the packaging element Psi 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 microM and 98 microM, respectively. Compound 9 binds with 4-7-fold higher affinity to SL3 RNA than to the other tetraloops found in Psi-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.
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Warui
authors.forename: Anne M
authors.initials: AM
authors.lastname: Baranger
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002151:Calorimetry; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D055029:Inverted Repeat Sequences / Q000235:genetics*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D020871:RNA Stability; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D017186:Titrimetry; D019065:Virus Assembly / Q000235:genetics
chemical_list: D000166:Acridines; D008024:Ligands; D012367:RNA, Viral; D054852:Small Molecule Libraries