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

Houssen, W. E. et al. (2014) An efficient method for the in vitro production of azol(in)e-based cyclic peptides. Angewandte Chemie (International Edition), 53(51), pp. 14171-14174. (doi: 10.1002/anie.201408082) (PMID:25331823) (PMCID:PMC4282754)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Koehnke, Professor Jesko
• Authors: Houssen, W. E., Bent, A. F., McEwan, A. R., Pieiller, N., Tabudravu, J., Koehnke, J., Mann, G., Adaba, R. I., Thomas, L., Hawas, U. W., Liu, H., Schwarz-Linek, U., Smith, M. C.M., Naismith, J. H., and Jaspars, M.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Angewandte Chemie (International Edition)
• Publisher: Wiley
• ISSN: 1433-7851
• ISSN (Online): 1521-3773
• Copyright Holders: Copyright © 2014 The Authors
• First Published: First published in Angewandte Chemie (International Edition) 53(51): 14171 –14174
• Publisher Policy: Reproduced under a Creative Commons licence