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

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Total chemical synthesis of glycocin F and analogues: S-glycosylation confers improved antimicrobial activity†
Chemical Science ( IF 7.6 ) Pub Date : 2018-01-12 00:00:00 , DOI: 10.1039/c7sc04383j
Zaid Amso ₁ , Sean W Bisset _{2,

3} , Sung-Hyun Yang ₁ , Paul W R Harris _{1,

3,

4} , Tom H Wright ₁ , Claudio D Navo ₅ , Mark L Patchett ₂ , Gillian E Norris _{2,

3} , Margaret A Brimble _{1,

3,

4}

Affiliation

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.

中文翻译：

糖蛋白 F 和类似物的全化学合成：S-糖基化可提高抗菌活性†

Glycocin F (GccF) 是一种独特的二糖基化细菌素肽，对多种革兰氏阳性菌具有有效且可逆的抑菌活性。 GccF 是“糖活性”细菌素的罕见例子，具有O连接的N -乙酰氨基葡萄糖 (GlcNAc) 和不寻常的S连接的 GlcNAc 部分，这些部分对于抗菌活性很重要。在本报告中，使用天然化学连接策略成功制备了糖蛋白 F，并将其折叠成其天然结构。化学合成的甘氨酸似乎比植物乳杆菌产生的重组材料活性稍高。第二代合成策略用于制备 2 个位点选择性“糖突变体”，其中包含两个S连接或两个O连接的 GlcNAc 部分；这些突变体用于探测每种类型的糖苷键对抑菌活性的贡献。用O-连接的GlcNAc替换残基43处的S-连接的GlcNAc降低了抗菌活性，而用S-连接的GlcNAc替换位置18处的O-连接的GlcNAc增加了生物活性，这表明S-糖苷键可以提供生物活性。获得更活性细菌素的启发途径。

更新日期：2018-01-12

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