Synthetic molecules that can mediate the coupled transport of Cl^(-) with K^(+) and/or Na+across the lipid bilayers have aroused great interest due to their potential as a novel therapeutic strategy by disrupting cell...Synthetic molecules that can mediate the coupled transport of Cl^(-) with K^(+) and/or Na+across the lipid bilayers have aroused great interest due to their potential as a novel therapeutic strategy by disrupting cellular ion homeostasis.Based on the structural advantages of molecular rotaxanes,we herein show that two rotaxane-based transporters[2]R and[3]R induce coupled K^(+)/Cl^(-) channel transport by introducing Cl^(-) recognition sites in the thread and K^(+) binding group in the wheel,respectively.The welldesigned molecular structures allow the insertion of unimolecular rotaxanes into the lipid bilayer,thus achieving effective ion transport by means of thermodynamically controlled movement and driven by the difference in ion concentration inside and outside the vesicles.In addition,the use of a three-component rotaxane can accelerate ion transport through a cooperative shuttlerelay mechanism in which two wheels move along the thread in the lipid membrane,thereby enabling[3]R to have higher ion transport capacity.This work represents a major advance in the use of rotaxane molecules to accomplish more complex and effective tasks.展开更多
基金supported by the National Natural Science Foundation of China(22171085)the Shanghai Science Technology Communication(21ZR1415500)Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,Grant 2021 Sci&Tech 03-28)。
文摘Synthetic molecules that can mediate the coupled transport of Cl^(-) with K^(+) and/or Na+across the lipid bilayers have aroused great interest due to their potential as a novel therapeutic strategy by disrupting cellular ion homeostasis.Based on the structural advantages of molecular rotaxanes,we herein show that two rotaxane-based transporters[2]R and[3]R induce coupled K^(+)/Cl^(-) channel transport by introducing Cl^(-) recognition sites in the thread and K^(+) binding group in the wheel,respectively.The welldesigned molecular structures allow the insertion of unimolecular rotaxanes into the lipid bilayer,thus achieving effective ion transport by means of thermodynamically controlled movement and driven by the difference in ion concentration inside and outside the vesicles.In addition,the use of a three-component rotaxane can accelerate ion transport through a cooperative shuttlerelay mechanism in which two wheels move along the thread in the lipid membrane,thereby enabling[3]R to have higher ion transport capacity.This work represents a major advance in the use of rotaxane molecules to accomplish more complex and effective tasks.
