Detergents for Dissociation of Lipid Rafts

DESCRIPTION (provided by applicant): Glycosphingolipids and cholesterol form associations with important signaling proteins, within biological membranes forming what are called "rafts". These rafts are characterized by their insolubility even in the presence of many detergents used in membrane chemistry to isolate proteins from the lipid components of membranes. Some of the most effective detergents for disrupting membrane rafts are derived from nature, e.g. the saponins and digitonin. Others are based on derivatized cyclodextrins such as methyl-beta-cyclodextrin (MBCD). None of the above are perfectly satisfactory. The saponins are of uncertain composition, digitonin is unstable in solution and highly toxic, and MBCD is expensive. A component of all rafts is cholesterol. This may account for the propensity of the steroid related structures of the saponins and digitonin to function as solubilizing agents. We propose to synthesize and test new detergents that incorporate cholesterol as the hydrophobic portion of the molecule. We will synthesize these new detergent molecules from inexpensive starting materials. The product materials will be water soluble and, since based on cholesterol, are expected to be non-toxic.