ABSTRACT
A class of unimolecular channels formed by pillararene-gramicidin hybrid molecules are presented. The charge status of the peptide domain in these channels has a significant impact on their ion transport and antimicrobial activity. These channels exhibited different membrane-association abilities between microbial cells and mammalian cells. One of the channels displayed a higher antimicrobial activity towards S. aureus (IC50 = 0.55 µM) and negligible hemolytic toxicity, showing potential to serve as a systemic antibiotic.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Calixarenes/pharmacology , Gramicidin/pharmacology , Ion Channels/antagonists & inhibitors , Staphylococcus aureus/drug effects , Animals , Anti-Bacterial Agents/chemistry , Calixarenes/chemistry , Dose-Response Relationship, Drug , Erythrocytes/drug effects , Gramicidin/chemistry , Ion Channels/metabolism , Ion Transport/drug effects , Microbial Sensitivity Tests , Molecular Structure , RatsABSTRACT
A class of artificial K+ channels formed by pillararene-cyclodextrin hybrid molecules have been designed and synthesized. These channels efficiently inserted into lipid bilayers and displayed high selectivity for K+ over Na+ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K+ over all alkali metal ions (selective sequence: K+ > Cs+ > Rb+ > Na+ > Li+ ), and is rarely observed for artificial K+ channels. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+ , and generated stable membrane potential across lipid bilayers.
