Subpicomolar Sensing of δ-Opioid Receptor Ligands by Molecular-Imprinted Polymers Using Plasmon-Waveguide Resonance Spectroscopy

Author(s): Devanathan, Savitha, Zdzislaw Salamon, Anoop Nagar, Subhash Narang, Donald Schleich, Paul Darman, Victor Hruby, Gordon Tollin

Journal: Anal. Chem. (2005) 77: 2569-2574.

Abstract:
Here we report, for the first time, the formation of a biomimetic covalently imprinted polymeric sensor for a target ligand, the δ-opioid G-protein coupled receptor agonist DPDPE, which reproducibly exhibits subpicomolar binding affinity in an aqueous environment. In addition to having a well-defined and homogeneous binding site, the imprinted polymer template is quite stable to storage in both the dry and wet states and has at least 6 orders of magnitude higher affinities than exhibited by similar peptide-based molecular-imprinted polymers (MIPs) thus far. A highly sensitive optical detection methodology, plasmon-waveguide resonance spectroscopy, was employed, capable of measuring binding in real time and discriminating between ligand molecules, without requiring labeling protocols (fluorophores or radioisotopes). The DPDPE-imprinted polymer showed a broad structure activity relationship profile, not unlike that found for protein receptors. Such sensitivity and robustness of MIPs suggests potential applications ranging from biowarfare agent detection to pharmaceutical screening.