Amso Zaid, Bisset Sean W, Yang Sung-Hyun, Harris Paul W R, Wright Tom H, Navo Claudio D, Patchett Mark L, Norris Gillian E, Brimble Margaret A
School of Chemical Sciences , The University of Auckland , 23 Symonds St , Auckland 1142 , New Zealand . Email:
Institute of Fundamental Sciences , Massey University , Colombo Rd , Palmerston North 4442 , New Zealand.
Chem Sci. 2018 Jan 12;9(6):1686-1691. doi: 10.1039/c7sc04383j. eCollection 2018 Feb 14.
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 -linked -acetylglucosamine (GlcNAc) and the unusual -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 . A second-generation synthetic strategy was used to prepare 2 site selective 'glyco-mutants' containing either two -linked or two -linked GlcNAc moieties; these mutants were used to probe the contribution of each type of glycosidic linkage to bacteriostatic activity. Replacing the -linked GlcNAc at residue 43 with an -linked GlcNAc decreased the antibacterial activity, while replacing -linked GlcNAc at position 18 with an -linked GlcNAc increased the bioactivity suggesting that the -glycosidic linkage may offer a biologically-inspired route towards more active bacteriocins.
糖霉素F（GccF）是一种独特的双糖基化细菌素肽，对多种革兰氏阳性菌具有强大且可逆的抑菌活性。GccF是“糖活性”细菌素的罕见例子，其α-连接的N-乙酰葡糖胺（GlcNAc）和不寻常的β-连接的GlcNAc部分对抗菌活性都很重要。在本报告中，使用天然化学连接策略成功制备了糖霉素F，并将其折叠成天然结构。化学合成的糖霉素似乎比从……产生的重组材料活性略高。采用第二代合成策略制备了2个位点选择性的“糖突变体”，分别含有两个α-连接或两个β-连接的GlcNAc部分；这些突变体用于探究每种糖苷键对抑菌活性的贡献。将第43位的α-连接的GlcNAc替换为β-连接的GlcNAc会降低抗菌活性，而将第18位的β-连接的GlcNAc替换为α-连接的GlcNAc会增加生物活性，这表明α-糖苷键可能为开发更具活性的细菌素提供一条受生物启发的途径。
