Issue 6, 2018

Total chemical synthesis of glycocin F and analogues: S-glycosylation confers improved antimicrobial activity

Abstract

Glycocin F (GccF) is a unique diglycosylated bacteriocin peptide that possesses potent and reversible bacteriostatic activity against a range of Gram-positive bacteria. GccF is a rare example of a ‘glycoactive’ bacteriocin, with both the O-linked N-acetylglucosamine (GlcNAc) and the unusual S-linked GlcNAc moiety important for antibacterial activity. In this report, glycocin F was successfully prepared using a native chemical ligation strategy and folded into its native structure. The chemically synthesised glycocin appeared to be slightly more active than the recombinant material produced from Lactobacillus plantarum. A second-generation synthetic strategy was used to prepare 2 site selective ‘glyco-mutants’ containing either two S-linked or two O-linked GlcNAc moieties; these mutants were used to probe the contribution of each type of glycosidic linkage to bacteriostatic activity. Replacing the S-linked GlcNAc at residue 43 with an O-linked GlcNAc decreased the antibacterial activity, while replacing O-linked GlcNAc at position 18 with an S-linked GlcNAc increased the bioactivity suggesting that the S-glycosidic linkage may offer a biologically-inspired route towards more active bacteriocins.

Graphical abstract: Total chemical synthesis of glycocin F and analogues: S-glycosylation confers improved antimicrobial activity

Supplementary files

Article information

Article type
Edge Article
Submitted
10 10 2017
Accepted
02 1 2018
First published
12 1 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2018,9, 1686-1691

Total chemical synthesis of glycocin F and analogues: S-glycosylation confers improved antimicrobial activity

Z. Amso, S. W. Bisset, S. Yang, P. W. R. Harris, T. H. Wright, C. D. Navo, M. L. Patchett, G. E. Norris and M. A. Brimble, Chem. Sci., 2018, 9, 1686 DOI: 10.1039/C7SC04383J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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