Using organic compounds to promote phospholipid flip-flop


Bradley D. Smith,, Department of Chemistry & Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556
The translocation of phospholipids from one side of a bilayer membrane to the other is inherently slow because of the high barrier for passage of the polar phospholipid head groups through the lipophilic interior of the membrane. There are several stages in the cell life cycle when phospholipids have to be translocated rapidly across the membrane and there is good evidence that this is process is mediated by membrane-bound translocase proteins. At present there is little information on how these proteins operate at the molecular level. In an effort to gain some mechanistic insight (and also to develop some practically useful molecules) we are evaluating the ability of various types of synthetic translocases. Previously, we have shown that appropriately designed anion receptors can form hydrogen bonds with the polar phospolipid head groups and then translocate them through membrane. The lecture will describe some new versions of this design principle. Also to be discussed are recent findings that a series of bolaamphiphiles can promote the flip-flop process. This is surprising because bolaamphilies are commonly viewed as membrane components that rigidify membranes and inhibit transport processes. This result may have relevance to the current debate on the origin of phospholipid translocation across biogenic membranes.

Membrane Active, Synthetic Organic Compounds
1:30 PM-5:05 PM, Sunday, 28 August 2005 Washington DC Convention Center -- Ballroom C, Oral

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005