title: Characterization and in vitro activity of a branched peptide boronic acid that interacts with HIV-1 RRE RNA.
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.
authors.affiliation: Department of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, United States.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Wynn
authors.affiliation: Department of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, United States.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, and The Myles H. Thaler Center for Human Retrovirus Research, University of Virginia, Charlottesville, VA 22908, United States.
authors.forename: Denis M
authors.initials: DM
authors.lastname: Tebit
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, and The Myles H. Thaler Center for Human Retrovirus Research, University of Virginia, Charlottesville, VA 22908, United States.
authors.forename: Laurie R
authors.initials: LR
authors.lastname: Gray
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, and The Myles H. Thaler Center for Human Retrovirus Research, University of Virginia, Charlottesville, VA 22908, United States.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Hammarskjold
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, and The Myles H. Thaler Center for Human Retrovirus Research, University of Virginia, Charlottesville, VA 22908, United States.
authors.forename: David
authors.initials: D
authors.lastname: Rekosh
authors.affiliation: Department of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, United States. Electronic address: santosw@vt.edu.
authors.forename: Webster L
authors.initials: WL
authors.lastname: Santos
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D001897:Boronic Acids / Q000737:chemistry* / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D019429:Integrase Inhibitors / Q000494:pharmacology; D019259:Lamivudine / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000068898:Raltegravir Potassium / Q000494:pharmacology; D020218:Response Elements; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; C000622600:BPBA3 peptide; D001897:Boronic Acids; D016655:HIV Core Protein p24; D019429:Integrase Inhibitors; D019151:Peptide Library; D010455:Peptides; D015363:Quinolones; D012367:RNA, Viral; D019259:Lamivudine; D000068898:Raltegravir Potassium; D015215:Zidovudine; C509700:elvitegravir
keywords: Boronic acids; Branched peptides; HIV-1; RRE RNA; p24 inhibition