Enzymatic macrocyclization of 1,2,3-triazole peptide mimetics
Date
04/05/2016Grant ID
NCB-TNT
BB/K015508/1
094476/Z/10/Z
BB/M028461/1
Metadata
Show full item recordAbstract
The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme-mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three anti-1,2,3-triazole moieties. The introduction of non-peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non-natural triazole-containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation.
Citation
Oueis , E , Jaspars , M , Westwood , N J & Naismith , J 2016 , ' Enzymatic macrocyclization of 1,2,3-triazole peptide mimetics ' , Angewandte Chemie , vol. 55 , no. 19 , pp. 5842-5845 . https://doi.org/10.1002/anie.201601564
Publication
Angewandte Chemie
Status
Peer reviewed
ISSN
0044-8249Type
Journal article
Rights
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://dx.doi.org/10.1002/anie.201601564 © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Description
This work was supported by the European Research Council (339367), UK Biotechnology and Biological Sciences Research Council (K015508/1), the Wellcome Trust (TripleTOF 5600 mass spectrometer (094476), the MALDI TOF-TOF Analyser (079272AIA), 700 NMR) and the EPSRC UK National Mass Spectrometry Facility at Swansea University. J.H.N. is a Royal Society Wolfson Merit Award Holder and 1000 talent scholar at Sichuan University.Collections
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