Abstract
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 language | English (US) |
|---|---|
| Pages (from-to) | 5462-5473 |
| Number of pages | 12 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 52 |
| Issue number | 17 |
| DOIs | |
| State | Published - Sep 10 2009 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery
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Identification of specific small molecule ligands for stem loop 3 ribonucleic acid of the packaging signal Ψ of human immunodeficiency virus-1. / Warui, Douglas; Baranger, Anne M.
In: Journal of Medicinal Chemistry, Vol. 52, No. 17, 10.09.2009, p. 5462-5473.Research output: Contribution to journal › Article
TY - JOUR
T1 - Identification of specific small molecule ligands for stem loop 3 ribonucleic acid of the packaging signal Ψ of human immunodeficiency virus-1
AU - Warui, Douglas
AU - Baranger, Anne M.
PY - 2009/9/10
Y1 - 2009/9/10
N2 - 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.
AB - 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.
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U2 - 10.1021/jm900599v
DO - 10.1021/jm900599v
M3 - Article
C2 - 19691339
AN - SCOPUS:69949106235
VL - 52
SP - 5462
EP - 5473
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 17
ER -