Suppression of epimerization by cupric (II) salts in peptide synthesis using free amino acids as amino components.
J Pept Res
; 53(3): 322-8, 1999 Mar.
Article
en En
| MEDLINE
| ID: mdl-10231721
An epimerization-free system for coupling N-protected peptides with free amino acids was developed. A number of inorganic substances were tested as epimerization suppressant additives during the coupling by various methods (carbodiimide plus additives, uronium salts, Woodward's reagent-K, isobutyl-chloroformate, etc.). Some of them (ZnCl2, RbClO4, LiCl, SnCl4, AlCl3, etc.) in combination with some coupling methods can guarantee coupling with minimal epimerization (D-epimer < 1%). But only a simultaneous use of 1-hydroxybenzotriazole and Cu2+ ions as additives in carbodiimide-mediated peptide couplings appeared to give a standard result (D-epimer < 0.1%). There was no epimerization even in the case when N-methyl amino acid (sarcosine) was used as an amino component, while in the absence of Cu2+ ions an unacceptable level of epimerization was observed (D-epimer, 22% for carbodiimide with the 1-hydroxybenzotriazole method). So far it has been considered that Cu2+ ions prevent obtaining peptides in high yields (< 90%) by various coupling methods. We have found that the use of 1-hydroxybenzotriazole, CuCl2 and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide instead of dicyclohexylcarbodiimide provides a possible method for obtaining the desired peptides in 90-99% yields without epimerization. All these results were shown by employing several model peptide couplings with free amino acids as amino components dissolved in an effective solvent system which readily dissolved them.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biosíntesis de Péptidos
/
Sales (Química)
/
Técnicas de Química Analítica
/
Cobre
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Pept Res
Asunto de la revista:
BIOQUIMICA
Año:
1999
Tipo del documento:
Article
Pais de publicación:
Dinamarca