近日，研究表明一种特殊类型的合成糖可能是对抗超级细菌的最新武器。
来自昆士兰大学和昆士兰Alchemia生物技术公司的科学家发现了一种潜在的新型抗生素，灵感来自于细菌产生的糖分子。
Matt Cooper教授和Johannes Zuegg 博士合作的该项研究发表在《Nature Communications》杂志上。
Matt Cooper教授说细菌自己的糖类成分不太可能对抗生素产生耐药性。
“细菌细胞壁与墙砖房子的墙类似，除了墙不是砂浆制成的而是由糖聚合物制成之外。”Cooper教授说。
“但如果你添加一个改良糖分子，它们就会停止链接，然后破坏细胞壁并杀死细菌。”
“细胞壁靶向抗生素如青霉素和万古霉素，但这里的区别是，我们正在阻止细胞壁连接过程中心重要的一部分。”
Zuegg博士说研究团队检查了数以百计Alchemia改良后的糖分子，目的是用来找到那些会杀死细菌并对人类细胞无毒的糖分子。
“大多数分子筛选成药物后是平面形状，而这些分子是三维立体状的。”Zuegg博士说。
“这意味着我们可以多种方式可以在三维空间中构建成千上万种不同组合的糖核心。”
PMC:
PMID:
Carbohydrate scaffolds as glycosyltransferase inhibitors with in vivo antibacterial activity
Johannes Zuegg, Craig Muldoon, George Adamson, Declan McKeveney, Giang Le Thanh, Rajaratnam Premraj, Bernd Becker, Mu Cheng, Alysha G. Elliott, Johnny X. Huang, Mark S. Butler, Megha Bajaj, Joachim Seifert, Latika Singh, Nicola F. Galley, David I. Roper, Adrian J. Lloyd, Christopher G. Dowson, Ting-Jen Cheng, Wei-Chieh Cheng et al.
The rapid rise of multi-drug-resistant bacteria is a global healthcare crisis, and new antibiotics are urgently required, especially those with modes of action that have low-resistance potential. One promising lead is the liposaccharide antibiotic moenomycin that inhibits bacterial glycosyltransferases, which are essential for peptidoglycan polymerization, while displaying a low rate of resistance. Unfortunately, the lipophilicity of moenomycin leads to unfavourable pharmacokinetic properties that render it unsuitable for systemic administration. In this study, we show that using moenomycin and other glycosyltransferase inhibitors as templates, we were able to synthesize compound libraries based on novel pyranose scaffold chemistry, with moenomycin-like activity, but with improved drug-like properties. The novel compounds exhibit in vitro inhibition comparable to moenomycin, with low toxicity and good efficacy in several in vivo models of infection. This approach based on non-planar carbohydrate scaffolds provides a new opportunity to develop new antibiotics with low propensity for resistance induction.