Characterization and in vitro activity of a branched peptide boronic acid that interacts with HIV-1 RRE RNA. Issue 17 (1st September 2016)

• Record Type: Journal Article
• Authors: Wynn, Jessica E.; Zhang, Wenyu; Tebit, Denis M.; Gray, Laurie R.; Hammarskjold, Marie-Louise; Rekosh, David; Santos, Webster L.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 17(2016)
• Page Start: 3947
• Page End: 3952
• Publication Date: 2016-09-01
• Subjects: HIV-1 -- RRE RNA -- Branched peptides -- Boronic acids -- p24 inhibition; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.04.009
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A branched peptide containing multiple boronic acids was found to bind RRE IIB selectively and inhibit HIV-1 p24 capsid production in a dose-dependent manner. Structure–activity relationship studies revealed that branching in the peptide is crucial for the low micromolar binding towards RRE IIB, and the peptide demonstrates selectivity towards RRE IIB in the presence of tRNA. Footprinting studies suggest a binding site on the upper stem and internal loop regions of the RNA, which induces enzymatic cleavage of the internal loops of RRE IIB upon binding.