Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization

Emilia Oueis, Brunello Nardone, Marcel Jaspars, Nicholas J. Westwood, James H. Naismith

Research output: Contribution to journalComment/debate

13 Citations (Scopus)
5 Downloads (Pure)

Abstract

Natural products comprise a diverse array of molecules, many of which are biologically active. Most natural products are derived 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 manmade 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, nine of which have been isolated and fully characterized.

Original languageEnglish
Pages (from-to)11-14
Number of pages4
JournalChemistryOpen
Volume6
Issue number1
Early online date13 Dec 2016
DOIs
Publication statusPublished - 1 Feb 2017

Fingerprint

Cyclic Peptides
Biological Products
Polyketides
Amino Acids
Thiazoles
Sugar Acids
Peptides
Polyethers
Fatty Acids
Molecules
Enzymes
Biosynthetic Pathways

Keywords

  • biotransformation
  • cyanobactin
  • hybrid macrocycles
  • macrocyclization
  • peptides

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization. / Oueis, Emilia; Nardone, Brunello; Jaspars, Marcel; Westwood, Nicholas J.; Naismith, James H.

In: ChemistryOpen, Vol. 6, No. 1, 01.02.2017, p. 11-14.

Research output: Contribution to journalComment/debate

Oueis, Emilia ; Nardone, Brunello ; Jaspars, Marcel ; Westwood, Nicholas J. ; Naismith, James H. / Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization. In: ChemistryOpen. 2017 ; Vol. 6, No. 1. pp. 11-14.
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note = "Acknowledgements We thank Dr. 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 Analyzer (079272AIA), 700 NMR], and the EPSRC UK National Mass Spectrometry Facility at Swansea University. J.H.N., M.A.J., and N.J.W. are named on patents that have been filed by St. Andrews and Aberdeen Universities to commercialize the enzymes (PatG) and (LynD) used in the study. No income derives from the patent.",
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