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

  1. Amso, Z. 3
  2. Bisset, S.W. 23
  3. Yang, S.-H. 3
  4. Harris, P.W.R. 3
  5. Wright, T.H. 3
  6. Navo, C.D. 1
  7. Patchett, M.L. 2
  8. Norris, G.E. 23
  9. Brimble, M.A. 3
  1. 1 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  2. 2 Massey University
    info

    Massey University

    Palmerston Norte, Nueva Zelanda

    ROR https://ror.org/052czxv31

  3. 3 University of Auckland
    info

    University of Auckland

    Auckland, Nueva Zelanda

    ROR https://ror.org/03b94tp07

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Revista:
Chemical Science

ISSN: 2041-6520

Año de publicación: 2018

Volumen: 9

Número: 6

Páginas: 1686-1691

Tipo: Artículo

DOI: 10.1039/C7SC04383J SCOPUS: 2-s2.0-85041725844 WoS: WOS:000424649300034 GOOGLE SCHOLAR

Otras publicaciones en: Chemical Science

Repositorio institucional: lock_openAcceso abierto Editor

Resumen

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. This journal is © The Royal Society of Chemistry. 2018.