Relative configuration of Cys‐Pro ester peptides in thioester formation

Abstract

A peptide containing a cysteinyl prolyl ester (CPE) moiety at the C-terminus (CPE peptide) was transformed into a diketopiperazine (DKP) thioester via an intramolecular N-S acyl shift reaction and was then used for peptide ligation. The difference in reactivity between the CPE peptide stereoisomers was examined. In reactions of the CPE peptides that contained L-Cys-L-Pro or D-Cys-D-Pro, the desired DKP thioester was formed at the preceding amino acid residue. On the other hand, in reactions of the CPE peptides that contained D-Cys-L-Pro or L-Cys-D-Pro, a thiolactone was formed at the C-terminal prolyl ester, and the ligation occurred at the C-terminal Pro residue. Using this reaction, it was possible to efficiently prepare a cyclic peptide.

Application of cysteinyl prolyl ester for the synthesis of cyclic peptides containing an RGD sequence and their biological activity measurement

“…Therefore, efficient methods have been developed to obtain cyclic peptides via the amide bond as well as the disulfide bond, oxime bond, and other bond formations ( Malesevic et al, 2004 ; Tulla-Puche and Barany, 2004 ; White and Yudin, 2011 ; Hemu et al, 2013 ; Terrier et al, 2017 ; Gless and Olsen, 2018 ; Shimodaira et al, 2018 ; Arbour et al, 2019 ; Chow et al, 2019 ; Reguera and Rivera, 2019 ; Sarojini et al, 2019 ; Serra et al, 2020 ). We also developed efficient cyclization methods based on our cysteinyl prolyl ester (CPE) ( Kawakami et al, 2022 ), which was originally developed for the synthesis of the peptide thioester ( Kawakami and Aimoto, 2007 ). In the CPE method, a peptide with the cysteinyl prolyl ester at the C-terminus is converted to the peptide thioester via the N-to-S acyl shift, followed by diketopiperazine formation.…”

Highly Efficient Photoelectrochemical Detection of Cystatin C Based on a Core–Shell MOF Nanocomposite with Biomimetic-Catalysis Amplification

“…The occurrence of the catalytic reaction depends on the binding of l -Cys to the active center of the hemin/G-quadruplex. 19 However, in the structure of l -cys/hemin/G-quadruplex, l -Cys spreads to the active center of hemin/G-quadruplex only by Brownian motion, 20 so the catalytic efficiency is limited by the relatively low binding affinity between hemin/G-quadruplex and l -Cys. However, the research team led by Li 19 confirms that the l -Cys-hemin/G-quadruplex possesses a better affinity to l -Cys compared with that of the hemin/G-quadruplex.…”