非天然型の側鎖構造を有するアミノ酸の設計・合成と機能性ペプチドへの応用

抄録

In recent years, the development of peptide chemistry has facilitated the synthesis of peptide libraries with diverse sequences. Along with this, peptides are widely used as probe molecules for elucidating biological functions and as tools for chemical biology research. However, there are limits to peptides consisting of only 20 types of proteinogenic α-amino acids. Such peptides are hydrolyzed by peptidases and proteases that are abundant in the body, and then, easily inactivate their functions. In addition, the secondary structure of short peptides is greatly fluctuated in the body, and thus, it is difficult to adopt a stable conformation. Against such background, the synthesis of non-proteinogenic amino acids (unnatural amino acids), the synthesis of peptide mimetics, and the techniques for controlling peptide secondary structures have been actively developed based on the synthetic organic chemistry approaches. We have been engaged in the design and synthesis of unnatural amino acids, the conformational analysis of their peptides, and research on their functionalization. This article describes unnatural amino acids that can change their side chain structures not only in amino acids themselves but also in peptides and control peptides secondary structures in response to the external environment. Furthermore, as an application study to the functional peptides using unnatural amino acids, I introduce cell-penetrating peptides and drug delivery peptides.