Derivatisable Cyanobactin Analogues: A Semisynthetic Approach

Emilia Oueis, Catherine Adamson, Greg Mann, Hannes Ludewig, Philip Redpath, Marie Migaud, Nicholas J. Westwood, James H. Naismith

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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. A combination of the chemical synthesis of peptides with enzymatic transformation allows the formation of patellamide-like unnatural cyclic peptides. These analogues can contain derivatisable unnatural amino acids along with the natural thiazoline motifs. Their derivatisation through the reactive unnatural groups is orthogonal and has many applications.

Original languageBritish English
Pages (from-to)2646-2650
Number of pages5
JournalChemBioChem
Volume16
Issue number18
DOIs
StatePublished - 14 Dec 2015

Keywords

  • click chemistry
  • cyclic peptides
  • enzymatic reactions
  • macrocyclisation
  • patellamides

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