Peptide chemical ligation inside living cells: in vivo generation of a circular protein domain

Julio A. Camarero, David Fushman, David Cowburn, Tom W. Muir

Research output: Contribution to journalArticle

47 Scopus citations


Here we describe the first example of a peptide chemical ligation reaction performed inside a living cell. A cell-based native chemical ligation approach was developed and used to generate a circular version of the N-terminal Src homology 3 (SH3) domain from the murine c-Crk adapter protein inside Escherichia coli cells. The in vivo cyclization reaction was extremely efficient and the resulting circular protein domain was fully biologically active and able to adopt the native SH3 folded structure. This work represents an important step towards the in vivo generation of small backbone cyclic peptides for use in basic biological research.

Original languageEnglish (US)
Pages (from-to)2479-2484
Number of pages6
JournalBioorganic and Medicinal Chemistry
Issue number9
StatePublished - Sep 22 2001
Externally publishedYes


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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