A synthetic route to human insulin using isoacyl peptides.
Angew Chem Int Ed Engl
; 53(15): 3983-7, 2014 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-24615765
ABSTRACT
The chemical synthesis of insulin has been a longstanding challenge, mainly because of the notorious hydrophobicity of the Aâ
chain and the complicated topology of this 51-mer peptide hormone consisting of two chains and three disulfide bonds. Reported herein is a new synthetic route utilizing the isoacyl peptide approach to address the hydrophobicity problems. The incorporation of isoacyl dipeptide segments into both A and Bâ
chains greatly improved their preparation and purification, and the RP-HPLC recovery of the chain ligation intermediates. The new route affords human insulin with a yield of 68 % based on the starting purified Aâ
chain and an overall yield of 24 % based on the substitution of the resin used for the preparation of Aâ
chain. To the best of our knowledge, this represents the most efficient route of human insulin chemical synthesis reported to date.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Insulina
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article