靶向折叠 RNA：一种支化肽硼酸与 HIV-1 RRE RNA 的大表面积结合。
Targeting folded RNA: a branched peptide boronic acid that binds to a large surface area of HIV-1 RRE RNA.
机构信息
Department of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, Virginia 24061, USA.
出版信息
Org Biomol Chem. 2013 Oct 7;11(37):6263-71. doi: 10.1039/c3ob41053f.
Abstract
On-bead high-throughput screening of a medium-sized (1000-2000 Da) branched peptide boronic 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 K(d) of 1.4 μM 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.
摘要
采用 bead 载体高通量筛选法，对包含 46656 条独特序列的中等大小（1000-2000Da）分支肽硼酸（BPBA）文库进行抗 HIV-1 RRE RNA 的筛选，得到了与低微摩尔范围结合亲和力的肽。特别是，BPBA1 与 RRE IIB 的 K(d)为 1.4 μM，对 RNA 比对 DNA 的偏好性（27 倍），对 RRE IIB 变体的选择性高达>75 倍。结构活性研究表明，硼酸部分和肽中的“分支”是与折叠 RNA 靶标高效结合和选择性的关键结构特征。BPBA1 能被 HeLa 和 A2780 细胞有效摄取。RNA 足迹研究表明，BPBA1 的结合位点涵盖了较大的表面区域，跨越了 RRE IIB 的上茎部以及内部环区域。
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