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Peptide Head‐to‐Tail Cyclization: A “Molecular Claw” Approach
Author(s) -
Yamagami Sayuri,
Okada Yohei,
Kitano Yoshikazu,
Chiba Kazuhiro
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100185
Subject(s) - chemistry , linker , peptide , combinatorial chemistry , cyclic peptide , amide , stereochemistry , peptide library , peptide sequence , biochemistry , computer science , gene , operating system
Both naturally occurring and artificial cyclic peptides are in high demand for a wide range of therapeutic applications due to the improvement of their enzymatic stability, cell permeability, and pharmacological activity compared to their linear counterparts. Among the simplest yet challenging cyclizations is the head‐to‐tail fashion, where linear peptides are cyclized via C‐ and N‐termini, since most current peptide synthesis has been dominated by the use of C‐terminal protecting supports. Herein, we demonstrate that a soluble‐tag‐assisted liquid‐phase peptide synthesis in combination with a backbone amide linker strategy is applicable to the head‐to‐tail cyclization. The use of an amide “N‐tag” instead of the general terminal C‐tag enables an effective head‐to‐tail cyclization on‐support. The key for successful cyclization is a tagging position that enables the center of the peptide to be grabbed.