In order to improve our understanding at the molecular level of how lipid organization determines membrane function, experiments are described to analyze lipid-lipid and lipid-protein interactions using spectral, kinetic, and permeability methods. For many of these studies, a series of phosphatidylcholine and sphingomyelin analogs will be synthesized. Special attention will be given to the preparation of compounds differing in the structure of the interfacial region. These analogs will be used to examine the importance of specific sites in the interactions between phospholipids, cholesterol, and proteins and in the rates of lipid movement between membranes. The properties of unusual, naturally occurring ether-linked phospholipids will also be studied. These studies are relevant to an understanding of the structures of both normal membranes and of membranes associated with several disease processes, such as atherosclerosis, where lipid accumulation takes place.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL016660-20
Application #
3485513
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-05-01
Project End
1996-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
20
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Queens College
Department
Type
Schools of Arts and Sciences
DUNS #
City
Flushing
State
NY
Country
United States
Zip Code
11367
Malewicz, Barbara; Valiyaveettil, Jacob T; Jacob, Kochurani et al. (2005) The 3-hydroxy group and 4,5-trans double bond of sphingomyelin are essential for modulation of galactosylceramide transmembrane asymmetry. Biophys J 88:2670-80
Waarts, Barry-Lee; Aneke, Onwuchekwa J C; Smit, Jolanda M et al. (2005) Antiviral activity of human lactoferrin: inhibition of alphavirus interaction with heparan sulfate. Virology 333:284-92
Lu, Xuequan; Bittman, Robert (2005) Synthesis of a photoactivatable (2S,3R)-sphingosylphosphorylcholine analogue. J Org Chem 70:4746-50
Lu, Xuequan; Byun, Hoe-Sup; Bittman, Robert (2004) Synthesis of l-lyxo-phytosphingosine and its 1-phosphonate analogue using a threitol acetal synthon. J Org Chem 69:5433-8
Li, Zaiguo; Mintzer, Evan; Bittman, Robert (2004) The critical micelle concentrations of lysophosphatidic acid and sphingosylphosphorylcholine. Chem Phys Lipids 130:197-201
Brockman, Howard L; Momsen, Maureen M; Brown, Rhoderick E et al. (2004) The 4,5-double bond of ceramide regulates its dipole potential, elastic properties, and packing behavior. Biophys J 87:1722-31
Sun, Chaode; Bittman, Robert (2004) An efficient preparation of isosteric phosphonate analogues of sphingolipids by opening of oxirane and cyclic sulfamidate intermediates with alpha-lithiated alkylphosphonic esters. J Org Chem 69:7694-9
Johnson, Charlene R; Chun, Jiong; Bittman, Robert et al. (2004) Intrinsic cytotoxicity and chemomodulatory actions of novel phenethylisothiocyanate sphingoid base derivatives in HL-60 human promyelocytic leukemia cells. J Pharmacol Exp Ther 309:452-61
McInerney, Gerald M; Smit, Jolanda M; Liljestrom, Peter et al. (2004) Semliki Forest virus produced in the absence of the 6K protein has an altered spike structure as revealed by decreased membrane fusion capacity. Virology 325:200-6
Bittman, Robert (2004) The 2003 ASBMB-Avanti Award in Lipids Address: Applications of novel synthetic lipids to biological problems. Chem Phys Lipids 129:111-31

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