Subpicomolar sensing of delta-opioid receptor ligands by molecular-imprinted polymers using plasmon-waveguide resonance spectroscopy.
Here we report, for the first time, the formation of a biomimetic covalently imprinted polymeric sensor for a target ligand, the delta-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.
Devanathan
Savitha
S
Department of Biochemistry and Molecular Biophysics, University of Arizona, Tucson, Arizona 85721, USA.
Salamon
Zdzislaw
Z
Nagar
Anoop
A
Narang
Subhash
S
Schleich
Donald
D
Darman
Paul
P
Hruby
Victor
V
Tollin
Gordon
G
D020881:Enkephalin, D-Penicillamine (2,5)- / Q000032:analysis*; D008024:Ligands; D009842:Oligopeptides / Q000032:analysis / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020349:Surface Plasmon Resonance / Q000379:methods*; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D008024:Ligands; D009842:Oligopeptides; D011108:Polymers; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; D020881:Enkephalin, D-Penicillamine (2,5)-