Targeting folded RNA: A branched peptide boronic acid that binds to large surface area of HIV-1 RRE RNA

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dc.contributorVirginia Tech. Department of Chemistryen
dc.contributorCenter for Drug Discoveryen
dc.contributor.authorZhang, Wenyuen
dc.contributor.authorBryson, David I.en
dc.contributor.authorCrumpton, Jason B.en
dc.contributor.authorWynn, Jessica E.en
dc.contributor.authorSantos, Webster L.en
dc.contributor.departmentChemistryen
dc.date.accessed2015-04-17en
dc.date.accessioned2015-04-20T18:49:34Zen
dc.date.available2015-04-20T18:49:34Zen
dc.date.issued2013-08-02en
dc.description.abstractOn-bead high-throughput screening of a medium-sized (1000_2000 Da) branched peptideboronic acid (BPBA) library consisting of 46 656 unique sequences against HIV-1 RRE RNA generated peptides with binding affinities in the low micromolar range. In particular, BPBA1 had a Kd of 1.4 _M with RRE IIB, preference for RNA over DNA (27 fold), and selectivity of up to >75 fold against a panel of RRE IIB variants. Structure_activity studies suggest that the boronic acid moiety and ͐branching in peptides are key structural features for efficient binding and selectivity for the folded RNA target. BPBA1 was efficiently taken up by HeLa and A2780 cells. RNA-footprinting studies revealed that the BPBA1 binding site encompasses a large surface area that spans both the upper stem as well as the internal loop regions of RRE IIB.en
dc.description.notesSupplementary information is included in a separate fileen
dc.description.sponsorshipNational Institutes of Health. National Institute of General Medical Sciences - award number RO1 GM093834en
dc.format.mimetypeapplication/pdfen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationZhang, W., Bryson, D. I., Crumpton, J. B., Wynn, J., & Santos, W. L. (2013). Targeting folded RNA: a branched peptideboronic acid that binds to a large surface area of HIV-1 RRE RNA. Organic & Biomolecular Chemistry, 11(37), 6263-6271. doi: 10.1039/C3OB41053Fen
dc.identifier.doihttps://doi.org/10.1039/C3OB41053Fen
dc.identifier.issn1477-0520en
dc.identifier.urihttp://hdl.handle.net/10919/51701en
dc.identifier.urlhttp://pubs.rsc.org/en/content/articlelanding/2013/ob/c3ob41053fen
dc.language.isoen_USen
dc.publisherThe Royal Society of Chemistryen
dc.rightsCreative Commons Attribution-NonCommercial 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en
dc.subjectRibonucleic acid (RNA)en
dc.subjectBoronic acid groupsen
dc.subjectPeptidesen
dc.titleTargeting folded RNA: A branched peptide boronic acid that binds to large surface area of HIV-1 RRE RNAen
dc.title.serialOrganic & Biomolecular Chemistryen
dc.typeArticle - Refereeden
dc.typeDataseten
dc.typeImageen
dc.type.dcmitypeTexten
dc.type.dcmitypeDataseten
dc.type.dcmitypeImageen

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