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首页> 外文期刊>Biochemistry >New binding specificities derived from min-23, a small cystine-stabilized peptidic scaffold
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New binding specificities derived from min-23, a small cystine-stabilized peptidic scaffold

机译：新的结合特异性衍生自min-23，一种小型的胱氨酸稳定的肽支架

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The randomization of both internal and surface residues in small protein domains followed by selection from a display library is emerging as a powerful strategy to obtain novel binding specificities. Small and stable scaffold motifs observed in disulfide-rich proteins are attractive because they are small, stable, and accessible to chemical synthesis. The elementary structural motif found in the squash trypsin inhibitor EETI-II (Ecballium elaterium trypsin inhibitor) is the cystine stabilized beta-sheet (CSB) motif, found in nearly 50% of all known small disulfide-rich protein families. We have used Min-23, a short 23-residue peptide containing the CSB motif and shown to be a stable autonomous folding unit and one of the smallest scaffolds described to date, as a scaffold for selection of new binding ligands. We demonstrate that the core CSB motif in Min-23 is permissive to loop insertion, using peptide epitopes from hemagglutinin (HA) and Gla-protein (E). A phage library of more than 108 different clones has been constructed by insertion of a randomized sequence on a β-turn of the Min-23 peptide. The selection of this library on a variety of 7 different targets allowed the isolation of 21 new specific binders, confirming the potential of Min-23 as a scaffold for the development of new ligands. The derived library is able to provide a wide range of novel compounds with possible applications in various biological and pharmaceutical areas.
机译：小蛋白结构域中内部和表面残基的随机化随后从展示库中进行选择正成为一种获得新颖结合特异性的有力策略。在富含二硫键的蛋白质中观察到的小而稳定的支架基序很有吸引力，因为它们小巧，稳定并且易于化学合成。在壁球胰蛋白酶抑制剂EETI-II（Ecballium elaterium胰蛋白酶抑制剂）中发现的基本结构基序是胱氨酸稳定的β-折叠（CSB）基序，在所有已知的富含小二硫键的小蛋白家族中占50％。我们已经使用Min-23（一种含有CSB基序的短23个残基的肽）作为选择新结合配体的支架，该肽是稳定的自主折叠单元，是迄今为止描述的最小的支架之一。我们证明了Min-23的核心CSB基序允许循环插入，使用来自血凝素（HA）和Gla蛋白（E）的肽表位。通过在Min-23肽的β角插入随机序列，已构建了超过108个不同克隆的噬菌体文库。在7种不同靶标上选择该文库可分离出21种新的特异性结合剂，从而证实了Min-23作为开发新配体的支架的潜力。衍生的文库能够提供广泛的新型化合物，并可能在各种生物和制药领域中应用。

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