This application is a request for an Independent Scientist Award (K02) to further Dr. Jane Aldrich's research in the area of drug abuse. Dr. Aldrich's long term goals are to use chemical approaches to study interactions between biologically important proteins and their ligands. The main focus of her research has been and will continue to be in the area of opioid peptides. The long term goals of this research program are to use opioid peptides as tools to obtain a better understanding of the interactions of these compounds with opioid receptors and to design new peptide and peptidomimetic ligands for opioid receptors. This research currently involves two major projects. One project focuses on the synthesis of peptide-based affinity labels for opioid receptors and the use of these covalent ligands to study opioid receptor structure and receptor-ligand interactions. The second project involves exploring the structural, conformational and topographical requirements for peptides, specifically dynorphin derivatives, for interaction with kappa opioid receptors. An Independent Scientist Award will allow Dr. Aldrich to expand her expertise in areas related to her research on opioid peptides. As part of this award she will gain experience in several areas, specifically using computational models of opioid receptors to examine possible receptor-ligand interactions and to design new opioid ligands; applying analytical techniques, specifically mass spectrometry, to studying ligand-receptor interactions; using combinatorial approaches to the design of novel ligands for opioid receptors; and applying protein isolation techniques to opioid receptors. In order to gain experience in these areas she will work with Dr. Simon (New York University Medical Center) as well as with her colleagues at the University of Maryland. Experience in these areas will complement her expertise in peptide chemistry and will enhance her ability to contribute to research in the area of drug abuse.
