Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization

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

*Corresponding author for this work

Research output: Contribution to journalComment/debate

13 Citations (Scopus)
6 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

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Keywords

  • biotransformation
  • cyanobactin
  • hybrid macrocycles
  • macrocyclization
  • peptides

ASJC Scopus subject areas

  • Chemistry(all)

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