Morimoto Jumpei, Yokomine Marin, Shiratori Yota, Ueda Takumi, Nakamuro Takayuki, Takaba Kiyofumi, Maki-Yonekura Saori, Umezawa Koji, Miyanishi Koichiro, Fukuda Yasuhiro, Watanabe Takumu, Suga Mayuko, Inayoshi Ayumi, Yoshida Takuya, Mizukami Wataru, Takeuchi Koh, Yonekura Koji, Nakamura Eiichi, Sando Shinsuke
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo 7-3-1 Hongo Bunkyo Tokyo 113-8656 Japan
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo 7-3-1 Hongo Bunkyo Tokyo 113-8656 Japan
Chem Sci. 2025 May 2. doi: 10.1039/d5sc01483b.
design of peptide shapes is of great interest in biomolecular science since the local peptide shapes formed by a short peptide chain in the proteins are often key to biological activities. Here, we show that the design of peptide shapes with sub-nanometer conformational control can be realized using peptides consisting of -methyl-l-alanine and -methyl-d-alanine residues. The conformation of -methyl-l/d-alanine residue is largely fixed because of the restricted bond rotation and hence can serve as a scaffold on which we can build a peptide into a designed shape. The local shape control by per-residue conformational restriction by torsional strains starkly contrasts with the global shape stabilization of proteins based on many remote interactions. The oligomers allow the bottom-up design of diverse peptide shapes with a small number of amino acid residues and would offer unique opportunities to realize the design of biofunctional molecules.
肽形状的设计在生物分子科学中备受关注，因为蛋白质中短肽链形成的局部肽形状通常是生物活性的关键。在此，我们表明，使用由α-甲基-L-丙氨酸和α-甲基-D-丙氨酸残基组成的肽，可以实现具有亚纳米构象控制的肽形状设计。由于键旋转受限，α-甲基-L/ D-丙氨酸残基的构象在很大程度上是固定的，因此可以作为一个支架，我们可以在其上将肽构建成设计的形状。通过扭转应变对每个残基的构象限制进行局部形状控制，与基于许多远程相互作用的蛋白质整体形状稳定形成鲜明对比。这些低聚物允许通过少量氨基酸残基进行自下而上的多种肽形状设计，并将为实现生物功能分子的设计提供独特的机会。
