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Chem Sci. 2018 Jan 12;9(6):1686-1691. doi: 10.1039/c7sc04383j. eCollection 2018 Feb 14.

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

Author information

1
School of Chemical Sciences , The University of Auckland , 23 Symonds St , Auckland 1142 , New Zealand . Email: m.brimble@auckland.ac.nz ; ; Tel: +64 9 3737599.
2
Institute of Fundamental Sciences , Massey University , Colombo Rd , Palmerston North 4442 , New Zealand.
3
Maurice Wilkins Centre for Molecular Biodiscovery , The University of Auckland , Private Bag 92019 , Auckland 1142 , New Zealand.
4
School of Biological Sciences , The University of Auckland , 3 Symonds St , Auckland 1142 , New Zealand.
5
Dept. Química , Universidad de La Rioja , Centro de Investigación en Síntesis Química , E-26006 Logroño , Spain.

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.

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