The objective of this proposal is to elucidate the interaction between cholesterol and human serum albumin (HSA). HSA has been implicated as a cholesterol shuttle between cells and lipoproteins. It may therefore play a role in cholesterol homeostasis, and thus have implications in heart disease. Several fluorescent models of cholesterol will be synthesized. These models are unlike those that are used currently in membrane studies. They will have chromophores that are spectrally distinct from aromatic residues in HSA while closely approximating cholesterol's structure. These models will allow the elucidation of the cholesterol binding sites in HSA, including both the number of sites and the binding affinities. Competitive binding studies with well known HSA ligands will establish the position of the binding sites and reveal allosteric interactions. In particular, a finding that certain drugs and/or fatty acids negatively affect cholesterol binding will suggest that these substances can have long term effects on arteriosclerosis. The interaction between cholesterol and human serum albumin (HSA) will be elucidated with new fluorescent cholesterol model compounds. The binding strengths and sites within HSA will be quantified and drug interactions will be revealed. The discovery of any negative drug interactions will suggest that these substances might accelerate arteriosclerosis. ? ? ?
