Synthesis of hybrid cyclopeptides through enzymatic macrocyclization
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Natural products comprise a diverse array of molecules many of which are biologically active. Most natural products derive from combinations of polyketides, peptides, sugars and fatty acid building blocks. Peptidic macrocycles have attracted attention as potential therapeutics possessing cell permeability, stability and easy to control variability. Here we show that enzymes from the patellamide biosynthetic pathway can be harnessed to make macrocycles that are hybrids of amino acids and a variety of man- made chemical building blocks, including aryl rings, polyethers and alkyl chains. We have made macrocycles with only three amino acids, one of which can be converted to a thiazoline or a thiazole ring. We report the synthesis of 18 peptide hybrid macrocycles, 9 of which have been isolated and fully characterized.
Oueis , E , Nardone , B , Jaspars , M , Westwood , N J & Naismith , J H 2017 , ' Synthesis of hybrid cyclopeptides through enzymatic macrocyclization ' ChemistryOpen , vol 6 , no. 1 , pp. 11-14 . DOI: 10.1002/open.201600134
© 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.
DescriptionWe thank G. Mann and Dr. A. Bent, for supplying the enzymes and the useful discussions, and Dr. T. Lebl for the useful NMR discussions. 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. JHN, MAJ and NJW are named on patents that have been filed by St Andrews and Aberdeen University to commercialize the enzymes (PatG) and (LynD) used in the study. No income derives from the patent.
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