Peptoid ligands that bind selectively to phosphoproteins.
Peptoid ligands that bind selectively to phosphoproteins.
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DOI：
10.1016/j.bmcl.2011.06.011
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发表时间：
2011-09-01
影响因子：
2.7
通讯作者：
Kodadek, Thomas
中科院分区：
文献类型：
--
作者：
Cai, Di;Lee, A-Young;Chiang, Cheng-Ming;Kodadek, Thomas
磷蛋白特异性抗体的合成等价物将是用于生物研究的有价值的试剂，因为这些抗体通常难以生产。蛋白质磷酸化被认为导致大多数底物蛋白质的显著构象变化。因此，一种方法可能是简单地筛选磷酸化状态的配体的组合文库，希望分离出与构象转变产生的口袋结合的配体。在这项研究中，我们通过筛选Brd4转录共激活蛋白磷酸化形式的配体的类肽文库来探测这种策略。我们发现，具有高选择性的结合磷酸化形式的Brd4的类肽确实可以在这个屏幕中分离。此外，这些配体不混杂地结合到其他磷蛋白。然而，在免疫亲和纯化类应用中使用这些试剂作为抗体替代物的尝试表明，它们的性能不如真正的抗体，并且需要显著的优化。这项研究强调了磷蛋白特异性抗体替代物的幼稚文库筛选策略的潜力和当前局限性。
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 transcriptional coactivator protein. We find that peptoids with high selectivity for binding to phopshorylated 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 naïve library screening strategy for phosphoprotein-specific antibody surrogates.
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影响因子：
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影响因子：
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通讯作者：
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DOI：
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