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Targeting the Tat-Binding Site of Bovine Immunodeficiency Virus TAR RNA with a Shape-Selective Rhodium Complex

Lim, Ai Ching and Barton, Jacqueline K. (1997) Targeting the Tat-Binding Site of Bovine Immunodeficiency Virus TAR RNA with a Shape-Selective Rhodium Complex. Bioorganic and Medicinal Chemistry, 5 (6). pp. 1131-1136. ISSN 0968-0896. https://resolver.caltech.edu/CaltechAUTHORS:20160324-071825486

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Abstract

The Tat-binding site of the bovine immunodeficiency virus TAR RNA hairpin has been targeted by Rh(phen)_2phi^(3+) (phen = phenanthroline, phi = 9,10-phenanthrenequinone diimine), a photochemical probe of RNA tertiary structure. The primary site cleaved by the rhodium complex, upon photoactivation, is U24, a base which participates in the novel base triple (with bases A13 and U10) characteristic of this folded RNA. Δ-Rh(phen)_2phi^(3+) binds to this site with an affinity of 2 × 10^6M^(−1). Upon mutation of U24 and A13 to A24 and U13, respectively, so that the RNA oligomer is unable to form the base triple, site-specific cleavage by the rhodium complex is abolished. Moreover, as determined through rhodium photocleavage, at a concentration of 20 μM, Rh(phen)_2phi^(3+) inhibits specific binding of BIV-Tat peptide (2 μM) to its target site. Thus the rhodium complex, in matching its shape to the opened major groove of the properly folded RNA, specifically targets its site and is able to compete for its target with the BIV-Tat peptide.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/S0968-0896(97)00049-7DOIArticle
http://www.sciencedirect.com/science/article/pii/S0968089697000497PublisherArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 1997 Elsevier Science Ltd. Received 10 September 1996; accepted 18 February 1997. Available online 26 March 1998. We are grateful to the National Institute of General Medical Sciences (GM33309) for their financial support of this research. In addition we thank Glaxo Research for fellowship support (A.C.L.).
Funders:
Funding AgencyGrant Number
National Institute of General Medical SciencesGM33309
Glaxo ResearchUNSPECIFIED
Issue or Number:6
Record Number:CaltechAUTHORS:20160324-071825486
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160324-071825486
Official Citation:Ai Ching Lim, Jacqueline K. Barton, Targeting the tat-binding site of bovine immunodeficiency virus TAR RNA with a shape-selective rhodium complex, Bioorganic & Medicinal Chemistry, Volume 5, Issue 6, June 1997, Pages 1131-1136, ISSN 0968-0896, http://dx.doi.org/10.1016/S0968-0896(97)00049-7. (http://www.sciencedirect.com/science/article/pii/S0968089697000497)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65640
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:24 Mar 2016 16:04
Last Modified:03 Oct 2019 09:49

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