Studies on the Synthetic Methodology of Head to Tail Cyclization of Linear Peptides

Autor: Mian Liu, Xing-ming Gao, Yan-chun Tang, Yun-hua Ye, Gui-Ling Tian
Rok vydání: 2003
Předmět:
Zdroj: International Journal of Peptide Research and Therapeutics. 10:571-579
ISSN: 1573-3904
1573-3149
DOI: 10.1007/s10989-004-2428-1
Popis: Our recent studies on the synthetic methodology of head to tail cyclization of linear peptides are summarized in this paper. Ten cyclopeptides including six cyclopentapeptides as candidates of LHRH antagonists, two cyclopentapeptides, and two cycloheptapeptides which were isolated from Chinese medicinal herbs were synthesized using an organic phosphorus reagent, DEPBT, and were selected as model peptides for studying the factors that influence the cyclization yields. Our results show that the coupling reagent choice and linear peptide sequence are the two most important considerations that determine the success or failure for a cyclization reaction. Effects of different metal ions on the cyclization were also studied. The results suggest that Na+ is suitable for promoting the cyclization of linear pentapeptides while bigger Cs+ is better for promotion of the ring closure of linear heptapeptides. Application of Pac ester in thioester method for synthesis of cyclopeptides was studied. N-protected amino acid and peptide thioesters with Pac group were readily purified in each step of synthesis. The Pac group was easy to remove with zinc powder in acetic acid and its flexibility allows elongatation of the peptide chain from either N-or C-terminal.
Databáze: OpenAIRE
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