Membrane Transporters For Anions That Use A Relay Mechanism

摘要

Synthetic bilayer membrane transporters are usually classified mechanistically as mobile carriers or as ion channels. A mobile carrier associates with a target ion to form a discrete supramolecular complex that diffuses across the membrane; whereas, an ion channel is a relatively immobile structure that spans the bilayer and allows a continuous flow of ions. In recent years there has been increased effort to design synthetic membrane transport systems for anions, especially Cl~-. One of the long-term goals of this work is to create transporter replacement therapies that can alleviate the symptoms of diseases caused by diminished levels of endogenous Cl~- transport (e.g., cystic fibrosis). The field of anion transport is still in its early stages with most published studies focusing on fundamental transport studies using model bilayer membranes. In terms of transporter designs, nearly all have been highly lipophilic compounds that partition strongly and nonselectively into any membrane.5 However, next-generation designs must begin to address the requirements for pharmaceutical success, including the following formulation features: (a) acceptable solubility in physiological solution, (b) appropriate cell targeting and subsequent membrane partitioning, (c) lengthy residence time in the apical plasma membrane of target cells. Suitably designed amphiphilic transporters are likely to exhibit these desirable properties; however, it is quite challenging to design amphiphilic transporters that operate by carrier or ion channel mechanisms. This quandary has prompted us to design a new type of membrane transporter that operates by a relay mechanism.