Nanomolar binding affinity of quinine-based antimalarial compounds by the cocaine-binding aptamer |
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Authors: | Sladjana Slavkovic Zachary R. Churcher Philip E. Johnson |
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Affiliation: | Department of Chemistry & Centre for Research on Biomolecular Interactions, York University, 4700 Keele St., Toronto, Ontario M3J 1P3 Canada |
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Abstract: | An unusual feature of the cocaine-binding aptamer is that it binds quinine much tighter than the ligand it was selected for, cocaine. Here we expand the repertoire of ligands that this aptamer binds to include the quinine-based antimalarial compounds amodiaquine, mefloquine, chloroquine and primaquine. Using isothermal titration calorimetry (ITC) we show that amodiaquine is bound by the cocaine-binding aptamer with an affinity of (7?±?4) nM, one of the tightest aptamer-small molecule affinities currently known. Amodiaquine, mefloquine and chloroquine binding are driven by both a favorable entropy and enthalpy of binding, while primaquine, quinine and cocaine binding are enthalpy driven with unfavorable binding entropy. Using nuclear magnetic resonance (NMR) and ITC methods we show that these ligands compete for the same binding sites in the aptamer. Our identification of such a tight binding ligand for this aptamer should prove useful in developing new biosensor techniques and applications using the cocaine-binding aptamer as a model system. |
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Keywords: | bp base pair DMSO dimethyl sulfoxide ITC isothermal titration calorimetry NMR nuclear magnetic resonance Tris 2-amino-2-hydroxymethyl-propane-1,3-diol Aptamer Isothermal titration calorimetry NMR spectroscopy Biomolecular interactions |
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