著者

仙石 徹

出版者

日本結晶学会

雑誌

日本結晶学会誌 (ISSN:03694585)

巻号頁・発行日

vol.63, no.3, pp.227-228, 2021-08-31 (Released:2021-09-02)

参考文献数

5

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Cyclic β-amino acids, such as (1R,2R)-2-aminocyclohexane carboxylic acid (ACHC), are known to induce compact conformation of peptides by forming turns and helices. Recently, a method to incorporate cyclic β-amino acids into peptides using ribosomes has been reported. Combining this method with the mRNA display method enabled the de novo discovery of macrocyclic peptides that contain cyclic β-amino acid residues and efficiently inhibit human coagulation factor XIIa (FXIIa). One such peptide, F3, potently inhibits FXIIa (Ki: 1.5 nM) and contains two ACHC residues. In the co-crystal structure of FXIIa-F3, F3 adopts an antiparallel β-hairpin structure stabilized by two ACHC residues. Despite its smaller size, F3 engages its target in a manner similar to that of natural protein-based inhibitors of serine proteases, demonstrating the utility of foldamer library consisting of macrocyclic peptides containing cyclic β-amino acids.