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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15HL089925-01
Application #
7304093
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Goldberg, Suzanne H
Project Start
2007-08-01
Project End
2011-07-31
Budget Start
2007-08-01
Budget End
2011-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$216,000
Indirect Cost
Name
College of William and Mary
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
074762238
City
Williamsburg
State
VA
Country
United States
Zip Code
23187
Green, Amy M; Abelt, Christopher J (2015) Dual-sensor fluorescent probes of surfactant-induced unfolding of human serum albumin. J Phys Chem B 119:3912-9
Naughton, Hannah R; Abelt, Christopher J (2013) Local solvent acidities in ýý-cyclodextrin complexes with PRODAN derivatives. J Phys Chem B 117:3323-7
Green, Amy M; Naughton, Hannah R; Nealy, Zachariah B et al. (2013) Carbonyl-twisted 6-acyl-2-dialkylaminonaphthalenes as solvent acidity sensors. J Org Chem 78:1784-9
Lopez, Nicholas A; Abelt, Christopher J (2012) Synthesis and Properties of Two PRODAN-based Fluorescent Models of Cholesterol. J Photochem Photobiol A Chem 238:35-40
Everett, Renata K; Nguyen, H A Ashley; Abelt, Christopher J (2010) Does PRODAN possess an O-TICT excited state? Synthesis and properties of two constrained derivatives. J Phys Chem A 114:4946-50
Everett, Renata; Hamilton, Jillian; Abelt, Christopher (2009) Preparation of 5-Bromo-2-naphthol: The Use of a Sulfonic Acid as a Protecting and Activating Group. Molbank 2009:M602