Investigating Molecular Recognition and Biological Function at Interfaces Using Antimicrobial Peptides.
EMSL Project ID
10595
Abstract
This research proposal features fundamental principles underlying biological function and mechanisms of action of peptides active at interfaces. The strategy for this project, which we initiated last summer, has been to use complementary solid-state Nuclear Magnetic Resonance (ssNMR) techniques on site-specific isotopically labeled peptides. A number of circular dichroism (CD) and solution NMR experiments have also been planned to help guide the ssNMR work. Syntheses, purification, and identification of the key peptides as well as their preparation for NMR experiments can and have been performed at Pacific Lutheran University (PLU, Tacoma, WA, http://www.plu.edu/). In order to permit progress towards the ssNMR-related goals of this proposal, we are applying for blocks of time on the EMSL 500 WB Varian Unity+ and 600 NB Varian Unity NMR spectrometers. As part of our plans, the mechanisms of action of piscidins, antimicrobial peptides from mast cells of fish, have been studied through the investigation of structure/dynamics/function relationships. These topics are addressed by a combination of robust ssNMR techniques, which I extensively used in my graduate and post-doctoral research. More precisely, we have performed REDOR distance measurements (13C to 15N) on labeled peptides interacting with hydrated lipid bilayers. Our very next step is to pursue REDOR measurements while varying sample conditions (pH, hydration, freeze-thaw cycles). In addition, two flat coil probes needed to obtain orientational constraints from oriented samples have been ordered thanks to some support I have recently received from the Research Corporation. Such probes are not available at the EMSL at this point in time and we are very enthusiastic at the idea of bringing them to the EMSL during the next scheduling period.
Understanding molecular recognition at interfaces as proposed here can provide some important knowledge needed to fight many diseases and design new drugs, including broad-spectrum ones. Beyond this scientific motivation, a paramount goal of this project is also to provide an environment in which undergraduate students can integrate learning and advanced research. Also, I am applying as the "primary author" but I would like two to three PLU students to be considered access too.
Access to the state of the art facility at EMSL would be pivotal to achieving my pursuits, both from research and educational standpoints. Thank you for your consideration.
Project Details
Project type
Capability Research
Start Date
2005-01-12
End Date
2005-07-21
Status
Closed
Released Data Link
Team
Principal Investigator