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

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Abstract

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.

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Authors and Affiliations

  1. The key Laboratory of Bioorganic Chemistry and Molecular Engineering, Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, P.R. China

    Yun-hua Yep, Xing-ming Gao, Mian Liu, Yan-chun Tang & Gui-ling Tian

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  1. Yun-hua Yep
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  2. Xing-ming Gao
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  3. Mian Liu
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  4. Yan-chun Tang
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  5. Gui-ling Tian
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Yep, Yh., Gao, Xm., Liu, M. et al. Studies on the Synthetic Methodology of Head to Tail Cyclization of Linear Peptides. Int J Pept Res Ther 10, 571–579 (2003). https://doi.org/10.1007/s10989-004-2428-1

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  • DOI: https://doi.org/10.1007/s10989-004-2428-1

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