Establishing the structure-activity relationship of teixobactin  

作　　者：Eilidh Matheson Kang Jin Xuechen Li 

机构地区：[1]Department of Chemistry,State Key Laboratory of Synthetic Chemistry,The University of Hong Kong,Hong Kong,China [2]Laboratory of Marine Drugs and Bioprodcuts,Qingdao National Laboratory for Marine Science and Technology,Qingdao 266237,China [3]School of Chemistry,University of Edinburgh,Edinburgh,UK

出　　处：《Chinese Chemical Letters》2019年第8期1468-1480,共13页中国化学快报（英文版）

基　　金：supported by the Research Grants Council of Hong Kong (No. C7038-15G);the Area of Excellence Scheme of the University of Grants Committee of Hong Kong (No. AoE/P-705/16)

摘　　要：In 2015,a new antimicrobial peptide agent was discovered,termed teixobactin.Over the past few years,the structure-activity relationship of teixobactin has been extensively studied.Here,the updated studies have been summarized to provide structure-activity relationship established to date.It can be seen that position 1,2,5 and 6 of teixobactin are not tolerant of diversion from the native amino acids.In positions 7 and 11,native amino acids give the highest activity but there is tolerance for other amino acids.Positions 3,4,9 and 10 are very tolerant of substitution while maintaining good potency and a broad activity spectrum.Activity does not depend on absolute stereochemistry,but on the relative stereochemistry and positions 1,4,5,and 8 must contain D-amino acids.The ring and tail structure are necessary for activity,macrolactone and lactam rings are both acceptable.Some teixobactin analogues show greater activity than native teixobactin.All conducted animal studies show positive results with no animal deaths.In 2015, a new antimicrobial peptide agent was discovered, termed teixobactin. Over the past few years,the structure-activity relationship of teixobactin has been extensively studied. Here, the updated studies have been summarized to provide structure-activity relationship established to date. It can be seen that position 1, 2, 5 and 6 of teixobactin are not tolerant of diversion from the native amino acids.In positions 7 and 11, native amino acids give the highest activity but there is tolerance for other amino acids. Positions 3, 4, 9 and 10 are very tolerant of substitution while maintaining good potency and a broad activity spectrum. Activity does not depend on absolute stereochemistry, but on the relative stereochemistry and positions 1, 4, 5, and 8 must contain D-amino acids. The ring and tail structure are necessary for activity, macrolactone and lactam rings are both acceptable. Some teixobactin analogues show greater activity than native teixobactin. All conducted animal studies show positive results with no animal deaths.

关 键 词：Teixobactin ANTIBACTERIAL PEPTIDE synthesis STRUCTURE-ACTIVITY RELATIONSHIP CYCLIC PEPTIDES 

分 类 号：O62[理学—有机化学]