Department of Medicinal Chemistry
Jane V. Aldrich
The design and synthesis of peptides and peptidomimetic analogs is the focus of research in the Aldrich laboratory. This research involves the examination of structure-activity relationships, primarily of opioid peptides, and the exploration of synthetic methodologies to prepare novel peptide and peptidomimetic analogs.
A major area of research in Dr. Aldrich's laboratory is the design and synthesis of peptidic ligands for kappa opioid receptors (KOR). The KOR is a potential target for the treatment of depression, anxiety and drug abuse, as well as for novel analgesics. The peptide ligands prepared include both analogs of the endogenous opioid peptide dynorphin as well as peptides with novel structures that have affinity for KOR. In addition to exploring the interactions of these peptides with opioid receptors in vitro, recent research has focused on identifying peptide KOR ligands with appropriate pharmacokinetic properties for use in vivo, with a focus on possible treatment of cocaine abuse. This includes evaluating the ability of the peptides to cross a model of the blood-brain barrier to reach KOR in the brain. This research has resulted in the identification of a peptide selective KOR antagonist that can be administered systemically and can prevent cocaine abuse relapse caused by stress (Aldrich et al., Proceedings of the National Academy of Sciences of the United States of America, in press).
Another major focus in the Aldrich laboratory is the design, synthesis and evaluation of labeled peptide derivatives. This includes peptides containing a label such as a fluorescent group that can be used for detection and reactive functionalities (affinity labels) that can be used to covalently attach the peptides to their targets in order to study receptor-ligand interactions at the molecular level.