Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia.
Lung Health Research Centre, Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia.
J Pept Sci. 2019 Sep;25(9):e3206. doi: 10.1002/psc.3206. Epub 2019 Aug 6.
Antimicrobial resistance is a serious threat to global human health; therefore, new anti-infective therapeutics are required. The cyclic depsi-peptide teixobactin exhibits potent antimicrobial activity against several Gram-positive pathogens. To study the natural product's mechanism of action and improve its pharmacological properties, efficient chemical methods for preparing teixobactin analogues are required to expedite structure-activity relationship studies. Described herein is a synthetic route that enables rapid access to analogues. Furthermore, our new N-methylated analogues highlight that hydrogen bonding along the N-terminal tail is likely to be important for antimicrobial activity.
抗微生物药物耐药性是对全球人类健康的严重威胁；因此，需要新的抗感染治疗方法。环状去肽肽替考拉宁对几种革兰氏阳性病原体具有很强的抗菌活性。为了研究天然产物的作用机制并改善其药理特性，需要有效的化学方法来制备替考拉宁类似物，以加速结构-活性关系的研究。本文描述了一种能够快速获得类似物的合成途径。此外，我们的新 N-甲基化类似物表明，N-末端尾部的氢键可能对抗菌活性很重要。
