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Chemical synthesis of a cyclotide via intramolecular cyclization of peptide O-esters

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  • Special Topic The Frontiers of Chemical Biology and Synthesis
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Abstract

Cyclotides constitute a fascinating family of circular proteins containing ca. 30 amino acid residues. They have a unique cyclic cysteine knot topology and exhibit remarkable thermal, chemical and enzymatic stabilities. These characteristics enable them to have a range of biological activities and promising pharmaceutical and agricultural applications. Here, we present a practical strategy for the chemical synthesis of cyclotides through the intramolecular ligation of fully unprotected peptide O-esters. This strategy involves the mild Fmoc solid-phase peptide synthesis of the peptide O-ester backbone, the head-to-tail cyclization of the cyclotide backbone by native chemical ligation, and the oxidative refolding to yield the natural knot protein. The simplicity and high efficiency of the strategy can be employed in the synthesis of artificial cyclotides for pharmaceutical applications.

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Authors and Affiliations

  1. Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China

    Ji-Shen Zheng, Hao-Nan Chang, Jing Shi & Lei Liu

  2. Department of Chemistry, Tsinghua University, Beijing, 100084, China

    Ji-Shen Zheng, Hao-Nan Chang, Jing Shi & Lei Liu

  3. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China

    Ji-Shen Zheng, Hao-Nan Chang, Jing Shi & Lei Liu

Authors
  1. Ji-Shen Zheng
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  2. Hao-Nan Chang
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  3. Jing Shi
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  4. Lei Liu
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Correspondence to Jing Shi or Lei Liu.

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Zheng, JS., Chang, HN., Shi, J. et al. Chemical synthesis of a cyclotide via intramolecular cyclization of peptide O-esters. Sci. China Chem. 55, 64–69 (2012). https://doi.org/10.1007/s11426-011-4434-4

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  • DOI: https://doi.org/10.1007/s11426-011-4434-4

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