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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA000393-03
Application #
6175088
Study Section
Special Emphasis Panel (ZDA1-MXS-M (01))
Program Officer
Hillery, Paul
Project Start
1998-09-01
Project End
2003-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
3
Fiscal Year
2000
Total Cost
$129,832
Indirect Cost
Name
University of Maryland Baltimore
Department
Other Health Professions
Type
Schools of Pharmacy
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Fang, Wei-Jie; Bennett, Marco A; Murray, Thomas F et al. (2011) Deletion of Ac-NMePhe(1) from [NMePhe(1) ]arodyn under acidic conditions, part 2: effects of substitutions on pharmacological activity. Biopolymers 96:103-10
Fang, Wei-Jie; Bennett, Marco A; Aldrich, Jane V (2011) Deletion of Ac-NMePhe(1) from [NMePhe(1) ]arodyn under acidic conditions, part 1: effects of cleavage conditions and N-terminal functionality. Biopolymers 96:97-102
Aldrich, Jane V; McLaughlin, Jay P (2009) Peptide kappa opioid receptor ligands: potential for drug development. AAPS J 11:312-22
Sinha, Bhaswati; Cao, Zhengyu; Murray, Thomas F et al. (2009) Discovery of dermorphin-based affinity labels with subnanomolar affinity for mu opioid receptors. J Med Chem 52:7372-5
Patkar, Kshitij A; Murray, Thomas F; Aldrich, Jane V (2009) The effects of C-terminal modifications on the opioid activity of [N-benzylTyr(1)]dynorphin A-(1-11) analogues. J Med Chem 52:6814-21
Fang, Wei-Jie; Cui, Yanjun; Murray, Thomas F et al. (2009) Design, synthesis, and pharmacological activities of dynorphin A analogues cyclized by ring-closing metathesis. J Med Chem 52:5619-25
Aldrich, Jane V; Kumar, Vivek; Murray, Thomas F et al. (2009) Dual labeled peptides as tools to study receptors: nanomolar affinity derivatives of TIPP (Tyr-Tic-Phe-Phe) containing an affinity label and biotin as probes of delta opioid receptors. Bioconjug Chem 20:201-4
Aldrich, Jane V; Kumar, Vivek; Dattachowdhury, Bhaswati et al. (2008) Solid Phase Synthesis and Application of Labeled Peptide Derivatives: Probes of Receptor-Opioid Peptide Interactions. Int J Pept Res Ther 14:315-321