Membrane transporters for anions that use a relay mechanism.
A new type of synthetic membrane transporter is described and shown to operate in vesicles by a relay mechanism. The transporter structure is a phosphatidylcholine derivative with a urea group appended to the end of its sn-2 acyl chain. The urea can bind a chloride ion at the membrane surface via hydrogen bonds and then relay it through the bilayer interior to an acceptor molecule located in the opposite membrane leaflet. Three phosphatidylcholine derivatives were studied and transport rates increased with transporter affinity for chloride. The results of various controls studies are consistent with an anion countertransport process using a relay mechanism and a kinetically active aggregate of two or four transporter molecules. Transport is inhibited if the transporter resides in only one leaflet of the membrane, if the bilayer is too thick, and if the counteranion is sulfate dianion. The expected favorable formulation properties of these amphiphilic compounds should facilitate efforts to transform them into tools for biomedical research and perhaps as therapeutic agents.
McNally
Beth A
BA
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
O'Neil
Edward J
EJ
Nguyen
Anh
A
Smith
Bradley D
BD
D000838:Anions / Q000378:metabolism*; D001692:Biological Transport; D001693:Biological Transport, Active; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019281:Dimerization; D015195:Drug Design; D006860:Hydrogen Bonding; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D013499:Surface Properties; D014508:Urea / Q000737:chemistry
D000838:Anions; D008051:Lipid Bilayers; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D014508:Urea