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首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Peptoid ligands that bind selectively to phosphoproteins.
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Peptoid ligands that bind selectively to phosphoproteins.

机译：与磷蛋白选择性结合的类肽配体。

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摘要

Synthetic equivalents of phosphoprotein-specific antibodies would be valuable reagents for biological research, since these antibodies can often be difficult to produce. Protein phosphorylation is thought to result in significant conformational changes in most substrate proteins. Therefore, one approach might be to simply screen combinatorial libraries for ligands to the phosphorylated state in the hope of isolating a ligand that binds to a pocket created by the conformational shift. In this study, we probe this strategy by screening a peptoid library for ligands to the phosphorylated form of the Brd4 chromatin adaptor and transcriptional coactivator protein. We find that peptoids with high selectivity for binding to the phosphorylation form of Brd4 can indeed be isolated in this screen. Moreover, these ligands do not bind promiscuously to other phospho-proteins. However, attempts to employ these reagents as antibody substitutes in an immunoaffinity purification-like application showed that they do not perform as well as bona fide antibodies and that significant optimization will be required. This study highlights the potential and current limitations of a naive library screening strategy for phosphoprotein-specific antibody surrogates.
机译：磷蛋白特异性抗体的合成等价物对于生物学研究将是有价值的试剂，因为这些抗体通常难以生产。人们认为蛋白质磷酸化会导致大多数底物蛋白质发生显着的构象变化。因此，一种方法可能是简单地筛选组合库中的配体是否处于磷酸化状态，以期希望分离出与构象转变所产生的口袋结合的配体。在这项研究中，我们通过筛选类肽库中Brd4染色质衔接子和转录共激活蛋白的磷酸化形式的配体来探索这一策略。我们发现具有高选择性结合Brd4磷酸化形式的类肽确实可以在此筛选中分离。此外，这些配体不会与其他磷酸蛋白混杂结合。但是，尝试在类似免疫亲和纯化的应用中将这些试剂用作抗体替代品，结果表明它们的性能不如真正的抗体，并且需要进行重大优化。这项研究突出了针对磷蛋白特异性抗体替代物的幼稚文库筛选策略的潜在和当前局限性。

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