The cyclization of peptides is a valuable strategy for the development of binding motifs to target proteins with improved affinity. Microtubules (MTs) are important targets for therapeutics, and a variety of MT-targeted drugs and peptides have recently been developed. We have previously designed a Tau-derived peptide ( TP ) that binds to the interior of MTs. In the present study, the development of a cyclic TP ( TCP ) for enhanced binding to tubulin and the stabilization of MTs are described. The fluorescently labeled cyclic peptide containing three glycine linkers ( TCP3-TMR ) exhibited a remarkably enhanced binding affinity to tubulin. The cyclic peptide was also demonstrated to stabilize MTs by enhancing polymerization and reducing depolymerization. Moreover, MTs were effectively formed by the treatment of cyclic peptides in the presence of guanosine triphosphate (GTP), while the linear peptide showed no such effect. These findings indicate that TCP is a useful binding motif that can stabilize MTs and is valuable for various therapeutic and material applications. Microtubules (MTs) consisting of tubulins are important targets of drugs for MT-related diseases. We have previously designed a linear Tau-derived peptide (TP) that binds to the interior of MTs. In this article, a cyclic TP (TCP) was developed for enhanced binding to tubulin and stabilization of MTs. The fluorescently labeled TCP exhibited a remarkably enhanced binding affinity to tubulin compared to the linear TP. The stabilization of MTs by binding of TCP was demonstrated, such as formation of typically unstable MTs in the presence of guanosine triphosphate.

中文翻译：

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用于稳定微管的环状 Tau 衍生肽

肽的环化是开发结合基序以提高亲和力的靶蛋白的重要策略。微管 (MTs) 是治疗的重要靶点，最近开发了多种 MT 靶向药物和多肽。我们之前设计了一种与 MT 内部结合的 Tau 衍生肽 (TP)。在本研究中，描述了用于增强与微管蛋白的结合和稳定 MT 的环状 TP (TCP) 的开发。含有三个甘氨酸接头 (TCP3-TMR) 的荧光标记环肽对微管蛋白的结合亲和力显着增强。环肽还被证明通过增强聚合和减少解聚来稳定 MT。而且，在三磷酸鸟苷 (GTP) 存在下处理环肽有效地形成了 MT，而线性肽则没有这种效果。这些发现表明 TCP 是一种有用的结合基序，可以稳定 MT，对各种治疗和材料应用都很有价值。由微管蛋白组成的微管 (MTs) 是治疗 MT 相关疾病的重要药物靶点。我们之前设计了一种线性 Tau 衍生肽 (TP)，它与 ​​MT 的内部结合。在本文中，开发了一种环状 TP (TCP) 以增强与微管蛋白的结合和稳定 MT。与线性 TP 相比，荧光标记的 TCP 对微管蛋白的结合亲和力显着增强。证明了通过结合 TCP 来稳定 MT，