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- Title
An Efficient Method for the In Vitro Production of Azol(in)e-Based Cyclic Peptides.
- Authors
Houssen, Wael E.; Bent, Andrew F.; McEwan, Andrew R.; Pieiller, Nathalie; Tabudravu, Jioji; Koehnke, Jesko; Mann, Greg; Adaba, Rosemary I.; Thomas, Louise; Hawas, Usama W.; Liu, Huanting; Schwarz‐Linek, Ulrich; Smith, Margaret C. M.; Naismith, James H.; Jaspars, Marcel
- 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.
- Subjects
CYCLIC peptides; AZOLES; HETEROCYCLIC compounds; ENZYMES; BIOCHEMICAL substrates
- Publication
Angewandte Chemie International Edition, 2014, Vol 53, Issue 51, p14171
- ISSN
1433-7851
- Publication type
Article
- DOI
10.1002/anie.201408082