In this grant application, a collaborative effort aimed at examining the conformational preferences of small peptides (as well as peptidomimetics) in the presence of small lipid vesicles, micelles, and reverse micelles is described. This research effort utilizes many spectroscopic techniques including nuclear magnetic resonance, circular dichroism, electron paramagetic resonance, fluorescence, infrared and Raman spectroscopy. For the refinement of the structures of the biomolecules, extensive computations will be carried out including molecular dynamics simulations, distance geometry-based calculations, and ab initio calculations for determination of the normal modes and principle stretching frequencies of the small peptides or peptidomimetics. From these studies the effects of the membrane environment, at differing levels of hydration, on the conformational preferences of small peptides and peptidomimetics will be ascertained. Considering that the receptor for many of these drug-candidates is membrane associated, this information is vital for the determination of the conformations first presented to the receptors during the initial binding process. In addition, reverse micelle-like environments have been utilized for delivery across membranes. Our results will shed insight into the structural preferences of the delivered material.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
1R03TW000980-01
Application #
2695497
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Michels, Kathleen M
Project Start
1999-09-30
Project End
2002-09-29
Budget Start
1999-09-30
Budget End
2000-09-29
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Brown University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912