分枝杆菌酸的化学结构，导致了布鲁里溃疡的发病原因。
Chemistry of mycolactones, the causative toxins of Buruli ulcer.
机构信息
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
出版信息
Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):6703-8. doi: 10.1073/pnas.1015252108. Epub 2011 Mar 7.
Abstract
Buruli ulcer is a severe and devastating skin disease caused by Mycobacterium ulcerans infection, yet it is one of the most neglected diseases. The causative toxin, referred to as mycolactone A/B, was isolated and characterized as a polyketide-derived macrolide in 1999. The current status of the mycolactone chemistry is described, highlighting the stereochemistry assignment of mycolactone A/B; total synthesis; the structure determination of mycolactone congeners from the human pathogen M. ulcerans, the frog pathogen Mycobacterium liflandii, and the fish pathogen Mycobacterium marinum; the structural diversity in the mycolactone class of natural products; the highly sensitive detection/structure-analysis of mycolactones; and some biological activity.
摘要
布鲁里溃疡是一种由溃疡分枝杆菌感染引起的严重且具有破坏性的皮肤疾病，但它是最被忽视的疾病之一。1999 年，分离并鉴定出致病毒素，称为 mycolactone A/B，它是一种聚酮衍生的大环内酯。本文描述了 mycolactone 的化学现状，重点介绍了 mycolactone A/B 的立体化学结构确定；全合成；从人类病原体溃疡分枝杆菌、青蛙病原体利福田地分枝杆菌和鱼类病原体海分枝杆菌中分离的 mycolactone 同系物的结构测定；mycolactone 类天然产物的结构多样性；mycolactone 的高灵敏度检测/结构分析；以及一些生物学活性。
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3
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4
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