磷脂酰甘油
达托霉素
对映体药物
立体化学
脂质体
化学
对映体
氢甲酰化
膜
磷脂
生物化学
磷脂酰胆碱
生物
细菌
对映选择合成
铑
催化作用
遗传学
万古霉素
金黄色葡萄球菌
作者
Ryan Moreira,Scott D. Taylor
标识
DOI:10.1002/anie.202114858
摘要
Abstract Daptomycin (dap) is an important antibiotic that interacts with the bacterial membrane lipid phosphatidylglycerol (PG) in a calcium‐dependent manner. The enantiomer of dap (ent‐dap) was synthesized and was found to be 85‐fold less active than dap against B. subtilis , indicating that dap interacts with a chiral target as part of its mechanism of action. Using liposomes containing enantiopure PG, we demonstrate that the binding of dap to PG, the structural transition that occurs upon dap binding to PG, and the subsequent oligomerization of dap, depends upon the configuration of PG, and that dap prefers the 1,2‐diacyl‐ sn ‐glycero‐3‐phospho‐1′‐ sn ‐glycerol stereoisomer (2 R ,2′ S configuration). Ent‐dap has a lower affinity for 2 R ,2′ S liposomes than dap and cannot oligomerize to the same extent as dap, which accounts for why ent‐dap is less active than dap. To our knowledge, this is the first example whereby the activity of an antibiotic depends upon the configuration of a lipid head group.
科研通智能强力驱动
Strongly Powered by AbleSci AI