Show simple item record

dc.contributor.authorBryson, David Irbyen
dc.date.accessioned2017-04-06T15:44:55Zen
dc.date.available2017-04-06T15:44:55Zen
dc.date.issued2012-03-19en
dc.identifier.otheretd-03252012-172449en
dc.identifier.urihttp://hdl.handle.net/10919/77327en
dc.description.abstractRNA is essential for the transfer of genetic information, as the central dogma of biology dictates. The role of RNA, however, is not limited to serving as an information shuttle between DNA and fully functional protein. Indeed, RNA has experienced a surge of interest in the field of chemical biology for its other critical roles in biology including those in control of transcription, translation, splicing, genetic replication, and catalysis. RNA has proven to be a difficult and complex target for the design of small molecular ligands because of its structural heterogeneity and conformational flexibility. Yet, the highly folded tertiary structures of these oligomers present unique scaffolds which designed ligands should be able to selectively target. To that end, two branched peptide libraries ranging in size from 4,096–46,656 unique sequences were screened for their ability to bind HIV-1 related RNA structures, the transactivation response element (TAR) and the Rev response element (RRE). In addition to discovering a mid-nanomolar branched peptide ligand for TAR, the first branched boronic acid peptide library designed to target RNA was screened for binding to RRE. Each of these efforts resulted in the identification of selective binders to their respective RNA targets, and the unnatural branching of these compounds was demonstrated to provide a multivalent binding interaction with the RNA. Furthermore, these compounds were shown to be cell permeable and displayed little to no cytotoxicity in HeLa and A2780 cells.en
dc.language.isoen_USen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectHigh Throughput Screeningen
dc.subjectCombinatorial Librariesen
dc.subjectBranched Peptidesen
dc.subjectMultivalencyen
dc.subjectCell Permeable Peptidesen
dc.subjectBoronen
dc.subjectRNAen
dc.subjectHIV-1en
dc.subjectMedium-Sized Ligandsen
dc.titleTargeting RNA Structures with Multivalent Branched Peptide Librariesen
dc.typeDissertationen
dc.contributor.departmentChemistryen
dc.description.degreePh. D.en
thesis.degree.namePh. D.en
thesis.degree.leveldoctoralen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.disciplineChemistryen
dc.contributor.committeechairSantos, Webster L.en
dc.contributor.committeememberCarlier, Paul R.en
dc.contributor.committeememberEtzkorn, Felicia A.en
dc.contributor.committeememberTanko, James M.en
dc.type.dcmitypeTexten
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-03252012-172449/en
dc.date.sdate2012-03-25en
dc.date.rdate2016-09-27en
dc.date.adate2012-05-03en


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record