Browsing by Author "Wynn, Jessica E."

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    Branched Peptide Boronic Acids (BPBAs): A Novel Mode of Binding Towards RNA
    Zhang, Wenyu; Bryson, David I.; Crumpton, Jason B.; Wynn, Jessica E.; Santos, Webster L. (The Royal Society of Chemistry, 2013-02-07)
    We report branched peptideboronic acids (BPBAs) that bind to RRE IIB from an on-bead high-throughput screening of a 3.3.4-library (46 656 compounds). We demonstrate that boronic acids are tunable moieties that afford a novel binding mode towards RNA.
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    Effect of intercalator and Lewis acid-base branched peptide complex formation: boosting affinity towards HIV-1 RRE RNA
    Wynn, Jessica E.; Zhang, Wenyu; Tebit, Denis M.; Gray, Laurie R.; Hammarskjold, Marie-Louise; Rekosh, David; Santos, Webster L. (Royal Society of Chemistry, 2016-06-06)
    High throughput screening of a 4096 compound library of boronic acid and acridine containing branched peptides revealed compounds that have dissociation constants in the low nanomolar regime for HIV-1 RRE IIB RNA. We demonstrate that branched peptide boronic acids A5, A6, and A7 inhibit the production of p24, an HIV-1 capsid protein, in a dose-dependent manner.
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    HIV-1 drug discovery: targeting folded RNA structures with branched peptides
    Wynn, Jessica E.; Santos, Webster L. (The Royal Society of Chemistry, 2015-04-28)
    Human immunodeficiency virus type 1 (HIV-1) is an RNA virus that is prone to high rates of mutation. While the disease is managed with current antiretroviral therapies, drugs with a new mode of action are needed. A strategy towards this goal is aimed at targeting the native three-dimensional fold of conserved RNA structures. This perspective highlights medium-sized peptides and peptidomimetics used to target two conserved RNA structures of HIV-1. In particular, branched peptides have the capacity to bind in a multivalent fashion, utilizing a large surface area to achieve the necessary affinity and selectivity toward the target RNA.
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    Targeting folded RNA: A branched peptide boronic acid that binds to large surface area of HIV-1 RRE RNA
    Zhang, Wenyu; Bryson, David I.; Crumpton, Jason B.; Wynn, Jessica E.; Santos, Webster L. (The Royal Society of Chemistry, 2013-08-02)
    On-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.