Polypeptide Preparation by ß-Lactone-Mediated Chemical Ligation.
Org Lett
; 26(26): 5436-5440, 2024 Jul 05.
Article
em En
| MEDLINE
| ID: mdl-38900935
ABSTRACT
Native chemical ligation (NCL) represents a cornerstone strategy in accessing synthetic peptides and proteins, remaining one of the most efficacious methodologies in this domain. The fundamental requisites for achieving a proficient NCL reaction involve chemoselective coupling between a C-terminal thioester peptide and a thiol-bearing N-terminal peptide. However, achieving coupling at sterically congested residues remains challenging. In addition, while most NCLs proceed without epimerization, ß-branched (e.g., Ile, Thr, Val) and Pro-derived C-terminal thioesters react slowly and can be susceptible to significant epimerization and hydrolysis. Herein, we report an epimerization-free NCL reaction via ß-lactone-mediated native chemical ligation which constructs sterically congested Thr residues. The constrained ring from the ß-lactone allows rapid peptide ligation without detectable epimerization. The method has a broad side-chain tolerance and was applied to the preparation of cyclic peptides and polypeptidyl thioester, which could be difficult to obtained otherwise.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Lactonas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article