Derivatisable cyanobactin analogues : a semisynthetic approach
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Many natural cyclic peptides have potent and potentially useful biological activities. Their use as therapeutic starting points is often limited by the quantities available, the lack of known biological targets and the practical limits on diversification to fine-tune their properties. We report the use of enzymes from the cyanobactin family to heterocyclise and macrocyclise chemically synthesised substrates so as to allow larger-scale syntheses and better control over derivatisation. We have made cyclic peptides containing orthogonal reactive groups, azide or dehydroalanine, that allow chemical diversification, including the use of fluorescent labels that can help in target identification. We show that the enzymes are compatible and efficient with such unnatural substrates. The combination of chemical synthesis and enzymatic transformation could help renew interest in investigating natural cyclic peptides with biological activity, as well as their unnatural analogues, as therapeutics.
Oueis , E , Adamson , C S , Mann , G , Ludewig , H , Naismith , J , Redpath , P , Migaud , M , Westwood , N J & Naismith , J 2015 , ' Derivatisable cyanobactin analogues : a semisynthetic approach ' ChemBioChem , vol 16 , no. 18 , pp. 2646-2650 . DOI: 10.1002/cbic.201500494
© 2015 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 (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This work was supported by the European Research Council (339367), UK Biotechnology and Biological Sciences Research Council (K015508/1) and the Wellcome Trust (Triple TOF 5600 mass spectrometer (094476), the MALDI TOF-TOF Analyser (079272AIA), 700 NMR and supported G.M. (097831)). J.H.N. is a Royal Society Wolfson Merit Award Holder and 1000 talent scholar at Sichuan University.
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