Screening of 5-HT1A Receptor Antagonists using Molecularly Imprinted Polymers

Molecular imprinting produces network polymers with recognition sites for imprint molecules. The high binding affinity and selectivity in conjunction with the polymers' physical robustness positions molecular imprinted polymers (MIPs) as candidates for use as preliminary screens in drug discove...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2007-02, Vol.129 (6), p.1680-1689
Main Authors: O'Connor, Naphtali A, Paisner, David A, Huryn, Donna, Shea, Kenneth J
Format: Article
Language:English
Subjects:
Binding Sites
Biomimetic Materials - chemistry
Biomimetic Materials - metabolism
Buspirone - chemistry
Buspirone - pharmacology
Chromatography, Affinity
Drug Evaluation, Preclinical - methods
Kinetics
Ligands
Models, Molecular
Molecular Conformation
Piperazines - chemistry
Piperazines - pharmacology
Polymethacrylic Acids - chemistry
Pyridines - chemistry
Pyridines - pharmacology
Receptor, Serotonin, 5-HT1A - chemistry
Receptor, Serotonin, 5-HT1A - metabolism
Serotonin 5-HT1 Receptor Antagonists
Serotonin Antagonists - chemistry
Serotonin Antagonists - pharmacology
Serotonin Receptor Agonists - chemistry
Serotonin Receptor Agonists - pharmacology
Spiperone - chemistry
Spiperone - pharmacology
Static Electricity
Structure-Activity Relationship
Thermodynamics
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Description
Summary:Molecular imprinting produces network polymers with recognition sites for imprint molecules. The high binding affinity and selectivity in conjunction with the polymers' physical robustness positions molecular imprinted polymers (MIPs) as candidates for use as preliminary screens in drug discovery. As such, MIPs can serve as crude mimics of native receptors. In an effort to evaluate the relationship between MIPs and native receptors, imprinted polymers for WAY-100635, an antagonist of the serotonin (5-HT) receptor subtype 5-HT1A were prepared. The resulting MIP P(WAY) was evaluated as an affinity matrix in the screening of serotonin receptor antagonists with known affinities for the native receptor. Rough correlations in affinity between the synthetic P(WAY) and native receptor 5-HT1A were found. These findings provide some support for the analogy between MIPs and native receptors and their possible use as surrogates.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja067276c