alexa Interaction of novel hybrid compounds with the D3 dopamine receptor: Site-directed mutagenesis and homology modeling studies.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Proteomics & Bioinformatics

Author(s): Kortagere S, Cheng SY, Antonio T, Zhen J, Reith ME,

Abstract Share this page

Abstract The dopamine D3 receptor has been implicated as a potential target for drug development in various complex psychiatric disorders including psychosis, drug dependence, and Parkinson's disease. In our overall goal to develop molecules with preferential affinity at D3 receptors, we undertook a hybrid drug development approach by combining a known dopamine agonist moiety with a substituted piperazine fragment. In the present study, three compounds produced this way with preferential D3 agonist activity, were tested at D3 receptors with mutations in the agonist binding pocket of three residues known to be important for agonist binding activity. At S192A and T369V, the hybrid agonist compounds produced an interaction profile in [(3)H]spiperone binding assays similar to that of the parent 5-OH-DPAT and 7-OH-DPAT molecules. The loss of affinity at the S192A mutant was most prominent for 5-OH-DPAT and its corresponding hybrid compound D237. D110N did not show any radioligand binding. Homology modeling indicated that 7-OH-DPAT-derived D315 uniquely shares H-bonding with Tyr365 which produced favorable interaction and no loss of H-bonding in the S192A mutant, suggesting that agonist activity may not be solely controlled by residues in the binding pocket. Copyright © 2010 Elsevier Inc. All rights reserved.
This article was published in Biochem Pharmacol and referenced in Journal of Proteomics & Bioinformatics

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 9th International Conference on Bioinformatics
    October 23-24, 2017 Paris, France
  • 9th International Conference and Expo on Proteomics
    October 23-25, 2017 Paris, France

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords