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Research at St Andrews

An efficient method for the in vitro production of Azol(in)e-based cyclic peptides

Research output: Contribution to journalArticlepeer-review

Author(s)

W.E. Houssen, A.F. Bent, A.R. McEwan, N. Pieiller, J. Tabudravu, J. Koehnke, G. Mann, R.I. Adaba, L. Thomas, U.W. Hawas, H. Liu, U. Schwarz-Linek, M.C.M. Smith, J.H. Naismith, M. Jaspars

School/Research organisations

Abstract

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6-9 residues representing 11 out of the 20 canonical amino acids.
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Details

Original languageEnglish
Pages (from-to)14171-14174
Number of pages4
JournalAngewandte Chemie International Edition
Volume53
Issue number51
Early online date21 Oct 2014
DOIs
Publication statusPublished - 15 Dec 2014

    Research areas

  • Cyanobactins, Cyclic peptides, Biosynthesis, Patellamides, Ribosomal peptides

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