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Cyclic Tau-derived peptides for stabilization of microtubules

Polymer Journal volume 52, pages 1143–1151 (2020)Cite this article

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Abstract

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.

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Acknowledgements

We thank Professor Y. Manabe and Professor K. Fukase (Osaka University) for the analysis of the peptides by LC-MS. This work was supported by KAKENHI (No. 17K14517 and 19K15699 for HI) from the Japan Society for the Promotion of Science (JSPS), the Inamori Foundation, and Konica Minolta Science and Technology Foundation for Konica Minolta Imaging Science Encouragement Award.

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Authors and Affiliations

  1. Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori, 680-8552, Japan

    Hiroshi Inaba, Miyuu Nagata, Kyeongmi Juliano Miyake & Kazunori Matsuura

  2. Centre for Research on Green Sustainable Chemistry, Tottori University, Tottori, 680-8552, Japan

    Hiroshi Inaba & Kazunori Matsuura

  3. Faculty of Science, Hokkaido University, Sapporo, 060-0810, Japan

    Arif Md. Rashedul Kabir, Akira Kakugo & Kazuki Sada

  4. Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, 060-0810, Japan

    Akira Kakugo & Kazuki Sada

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  1. Hiroshi Inaba
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Correspondence to Hiroshi Inaba or Kazunori Matsuura.

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Inaba, H., Nagata, M., Miyake, K.J. et al. Cyclic Tau-derived peptides for stabilization of microtubules. Polym J 52, 1143–1151 (2020). https://doi.org/10.1038/s41428-020-0356-3

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