Pore-Forming Amphiphiles

Lehigh University, Bethlehem PA

Investigators

Abstract

This proposal addresses the synthesis and study of cholic acid-dendrimer conjugates designed to generate through-membrane pores of tunable dimensions in phospholipid bilayers. The effect of increasing the number of choloyl units on sodium and lithium transport and on pore sizes will be studied. Introduction of proton-ionizable groups is expected to favor formation of pores in negatively charged liposomes relative to ones bearing a zwitterionic surface. In studies to be carried out by undergraduate students "en masse," immobilization of a conjugate formed from cholic acid, a persulfated form of cholic acid, and putrescine on an ion exchange resin will lead to a "hydrophobic sponge" with improved molecular absorption properties. With the support of the Organic and Macromolecular Chemistry Program, Professor Steven L. Regen, of the Department of Chemistry at Lehigh University, is studying the synthesis and properties of molecules designed to create perforations in cellular membranes. Formation of such pores in living cells can be lethal, and biological molecules which cause pore formation, such as amphotericin, represent effective antibiotics. Professor Regen's studies of design strategies for effecting pore formation represent foundational research that will provide the platform for future developments of new cytotoxic agents. Portions of the research will be carried out by large teams of undergraduate researchers.