Target-oriented design and biosynthesis of thiostrepton-derived thiopeptide antibiotics with improved pharmaceutical properties

Literature Information

Publication Date 2014-12-05
DOI 10.1039/C4QO00288A
Impact Factor 5.281
Authors

Shoufeng Wang, Qingfei Zheng, Jianfeng Wang, Zhixiong Zhao, Qingye Li, Yunsong Yu, Renxiao Wang


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Abstract

Thiostrepton is a potent archetypal thiopeptide antibiotic. According to its mechanism known to target bacterial ribosome, we show here a rational design upon modeling of this molecule into the ribosome complex and an effective biosynthesis of new thiopeptide antibiotics through regioselective modifications. The resulting derivatives exhibit a series of anticipated and unanticipated pharmaceutical advantages, including improvement in activity against a number of drug-resistant pathogens and in water solubility that has largely affected the clinical use of thiostrepton.

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Organic Chemistry Frontiers

Organic Chemistry Frontiers
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Organic Chemistry Frontiers publishes high-quality research from across organic chemistry. Emphases are placed on studies that make significant contributions to the field of organic chemistry by reporting either new or significantly improved protocols or methodologies. Topics include, but are not limited to the following: Organic synthesis Development of synthetic methodologies Catalysis Natural products Functional organic materials Supramolecular and macromolecular chemistry Physical and computational organic chemistry

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