The overall objective of this research is to gain quantitative insight into lipid lipid and lipid-protein interactions in the fluid bilayer state, using a combination of synthetic-organic chemistry, physical-organic chemistry, and the nearest-neighbor recognition method. The long-term goal of this program is to develop a fundamental understanding of the two- dimensional organization of fluid bilayers, which will help to bring exploitable targets in biological membranes (e.g., the plasma membrane of cancer cells, bacterial cells, and fungal cells) into sharper focus. Such insight will assist the rational design of novel classes of therapeutic agents.
The specific aims of the current funding period include: (1) mapping out phase diagrams of sphingolipid/glycerophospholipid/cholesterol, and analogous glycerophospholipid/glycerophospholipid/cholesterol, bilayers by use of nearest-neighbor recognition methods; (2) defining the nearest-neighbor preference of cholesterol with respect to a sphingolipid and a glycerophospholipid; (3) defining the influence of a carbohydrate head group in promoting self-aggregation; (4) testing for transmembrane-protein recognition of a phospholipid based on hydrophobic matching, (5) measuring the sensitivity of lipid transmembrane-protein interactions toward the presence of cholesterol, (6) developing a methodology that can be used to study lipid communication between adjoining monolayers, and (7) detecting transmembrane recognition of neighboring lipids.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056149-08
Application #
6891927
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Chin, Jean
Project Start
1998-05-01
Project End
2007-04-30
Budget Start
2005-05-01
Budget End
2007-04-30
Support Year
8
Fiscal Year
2005
Total Cost
$269,127
Indirect Cost
Name
Lehigh University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
808264444
City
Bethlehem
State
PA
Country
United States
Zip Code
18015
Daly, Trevor A; Almeida, Paulo F; Regen, Steven L (2012) Sorting of lipidated peptides in fluid bilayers: a molecular-level investigation. J Am Chem Soc 134:17245-52
Daly, Trevor A; Wang, Minghui; Regen, Steven L (2011) The origin of cholesterol's condensing effect. Langmuir 27:2159-61
Turkyilmaz, Serhan; Almeida, Paulo F; Regen, Steven L (2011) Effects of isoflurane, halothane, and chloroform on the interactions and lateral organization of lipids in the liquid-ordered phase. Langmuir 27:14380-5
Turkyilmaz, Serhan; Mitomo, Hideyuki; Chen, Wen-Hua et al. (2010) Phospholipid complexation of general anesthetics in fluid bilayers. Langmuir 26:5309-11
Janout, Vaclav; Turkyilmaz, Serhan; Wang, Minghui et al. (2010) An upside down view of cholesterol's condensing effect: does surface occupancy play a role? Langmuir 26:5316-8
Turkyilmaz, Serhan; Chen, Wen-Hua; Mitomo, Hideyuki et al. (2009) Loosening and reorganization of fluid phospholipid bilayers by chloroform. J Am Chem Soc 131:5068-9
Mitomo, Hideyuki; Chen, Wen-Hua; Regen, Steven L (2009) Reduced sterol-phospholipid recognition in curved fluid bilayers. Langmuir 25:4328-30
Mitomo, Hideyuki; Chen, Wen-Hua; Regen, Steven L (2009) Oxysterol-induced rearrangement of the liquid-ordered phase: a possible link to Alzheimer's disease? J Am Chem Soc 131:12354-7
Zhang, Jianbing; Jing, Bingwen; Janout, Vaclav et al. (2007) Detecting cross talk between two halves of a phospholipid bilayer. Langmuir 23:8709-12
Zhang, Jianbing; Cao, Honghua; Regen, Steven L (2007) Cholesterol-phospholipid complexation in fluid bilayers as evidenced by nearest-neighbor recognition measurements. Langmuir 23:405-7

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