A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide

Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selectiv...

Descripción completa

Detalles Bibliográficos
Autores principales: Qiu, Zhonghao, Dai, Xiandong, Fan, Chongxu, Cao, Ying, Lv, Zirui, Liang, Xingyong, Meng, Fanhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9919235/
https://www.ncbi.nlm.nih.gov/pubmed/36770675
http://dx.doi.org/10.3390/molecules28031007
Descripción
Sumario:Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selective formation of three disulfide bonds in satisfactory overall yields via mild oxidation reactions of the solid phase and liquid phase, using 4-methoxytrityl (Mmt), diphenylmethyl (Dpm) and 2-nitrobenzyl (O-NBn) protecting groups of cysteine as substrate, respectively.

Ejemplares similares