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Abstract
Grant Number: 1R43GM069021-01 PI Name: KEYES, MELVIN H. PI Email: anatrac434@aol.com PI Title: Project Title: Detergents for Dissociation of Lipid Rafts Abstract: 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.
Thesaurus Terms:
chemical synthesis, cholesterol, detergent, hydropathy, water solubility
chemical structure function, digitonin, physical property
biotechnology
Institution: ANATRACE, INC. 1280 DUSSEL DR MAUMEE, OH 43537 Fiscal Year: 2003 Department: Project Start: 15-SEP-2003 Project End: 14-MAR-2004 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: ZRG1
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