? This application is a competitive renewal of 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 design and use new opioid peptide and peptidomimetic ligands as pharmacological tools to obtain a better understanding of opioid peptide-receptor interactions. The proposed research uses a combination of chemical, pharmacological and computational techniques, with the rationale that the information obtained from these complimentary methodologies will limit the number of possibilities for interactions of the peptides with receptor residues, greatly facilitating the development of models for the peptides bound to opioid receptors. ? ? Continuation of the Independent Scientist Award will allow Dr. Aldrich to expand her expertise in several areas related to her research on opioid peptides. These areas include synthesis (including stereoselective synthesis) of novel amino acid analogs for incorporation into opioid peptide analogs, gaining familiarity with molecular biological techniques to study opioid receptors, and obtaining additional experience with protein characterization by mass spectrometry. Experience in these areas will be synergistic with Dr. Aldrich's expertise in peptide chemistry and significantly enhance her contributions to research in the area of drug abuse. ? ? ? ?