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 journalArticle

13 Citations (Scopus)
257 Downloads (Pure)

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.

Original languageEnglish
JournalChemBioChem
Volume16
Issue number18
Early online date10 Nov 2015
DOIs
Publication statusPublished - 14 Dec 2015

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