Design and Synthesis of Photoaffinity-labeling Ligands of the L-prolyl-l-leucylglycinamide Binding Site Involved in the Allosteric Modulation of the Dopamine Receptor.
From: Department of Medicinal Chemistry, University of Minnesota, 308 Harvard St. SE, Minneapolis, Minnesota 55455-0343, USA.
Journal of medicinal chemistry
- Publish Date: Jan 2006
- ISSN: 0022-2623
- Volume: 49
- Issue: 1
- Pages: 307-17
- Medium: Print
- Language: English
- Citation (JAMA): Fisher Abigail, Mann Amandeep, Verma Vaneeta, et al. Design and Synthesis of Photoaffinity-labeling Ligands of the L-prolyl-l-leucylglycinamide Binding Site Involved in the Allosteric Modulation of the Dopamine Receptor.. J. Med. Chem. Jan 2006;49:307-17
Abstract
Pro-Leu-Gly-NH(2) (PLG), in addition to its endocrine effects, possesses the ability to modulate dopamine D(2) receptors within the central nervous system. However, the precise binding site of PLG is unknown. Potential photoaffinity-labeling ligands of the PLG binding site were designed as tools to be used in the identification of the macromolecule that possesses this binding site. Six different photoaffinity-labeling ligands were designed and synthesized on the basis of the gamma-lactam PLG peptidomimetic 1. The 4-azidobenzoyl and 4-azido-2-hydroxybenzoyl photoaffinity-labeling moieties were placed at opposite ends of PLG peptidomimetic 1 to generate a series of ligands that potentially could be used to map the PLG binding site. All of the compounds that were synthesized possessed activity comparable to or better than PLG in enhancing [(3)H]-N-propylnorapomorphine agonist binding to dopamine receptors. Photoaffinity ligands that were cross-linked to the receptor preparation produced a modulatory effect that was either comparable to or greater than the increase in agonist binding produced by the respective ligands that were not cross-linked to the dopamine receptor. The results indicate that these photoaffinity-labeling agents are binding at the same allosteric site as PLG and PLG peptidomimetic 1.
Mesh Headings (Keywords): Allosteric Regulation, Animals, Apomorphine, Binding Sites, Cattle, Dopamine Agents, Drug Design, Ligands, MSH Release-Inhibiting Hormone, Molecular Conformation, Photoaffinity Labels, Receptors, Dopamine D2, Structure-Activity Relationship
Check for Full Text / PubMed Unique Identifier (PMID): 16392815
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.