The specific aims of this research include the synthesis of a homologous series of sterol conjugates by use of amino- and amino acid-derived hexa(ethylene glycol), hexaglycine, hexaalanine and spermine; the preparation of a macrocyclic sterol dimer containing a tridecaethylene glycol chain; the synthesis of a series of oligomers based on spermine and substituted cholic acid; and, the examination of ion transport kinetics and pore-forming properties of each of the above amphiphiles by means of 23Na Nuclear Magnetic Resonance (NMR) spectroscopy. With this award, the Organic Dynamics Program is supporting the research of Dr. Steven L. Regen of the Department of Chemistry at Lehigh University. Professor Regen will focus his work on defining the influence that charge, hydrogen bonding, end group interactions and oligomerization have on the pore-forming properties of sterol-based compounds known as amphiphiles. The goal of the work is to learn how to control the monomer-aggregate equilibrium of such amphiphiles within lipid bilayers that mimic the plasma membrane of bacterial, fungal and mammalian cells. The long range goal of the work is to provide a foundation for the rational design of new classes of antibiotics.
