title: Structure-affinity relationship of the cocaine-binding aptamer with quinine derivatives.
abstract: In addition to binding its target molecule, cocaine, the cocaine-binding aptamer tightly binds the alkaloid quinine. In order to understand better how the cocaine-binding aptamer interacts with quinine we have used isothermal titration calorimetry-based binding experiments to study the interaction of the cocaine-binding aptamer to a series of structural analogs of quinine. As a basis for comparison we also investigated the binding of the cocaine-binding aptamer to a set of cocaine metabolites. The bicyclic aromatic ring on quinine is essential for tight affinity by the cocaine-binding aptamer with 6-methoxyquinoline alone being sufficient for tight binding while the aliphatic portion of quinine, quinuclidine, does not show detectable binding. Compounds with three fused aromatic rings are not bound by the aptamer. Having a methoxy group at the 6-position of the bicyclic ring is important for binding as substituting it with a hydrogen, an alcohol or an amino group all result in lower binding affinity. For all ligands that bind, association is driven by a negative enthalpy compensated by unfavorable binding entropy.
authors: Department of Chemistry & Centre for Research on Biomolecular Interactions, York University, 4700 Keele St., Toronto, Ontario M3J 1P3, Canada.
authors: Sladjana
authors: S
authors: Slavkovic
authors: Department of Chemistry & Centre for Research on Biomolecular Interactions, York University, 4700 Keele St., Toronto, Ontario M3J 1P3, Canada.
authors: Merve
authors: M
authors: Altunisik
authors: Department of Chemistry & Centre for Research on Biomolecular Interactions, York University, 4700 Keele St., Toronto, Ontario M3J 1P3, Canada.
authors: Oren
authors: O
authors: Reinstein
authors: Department of Chemistry & Centre for Research on Biomolecular Interactions, York University, 4700 Keele St., Toronto, Ontario M3J 1P3, Canada. Electronic address: pjohnson@yorku.ca.
authors: Philip E
authors: PE
authors: Johnson
mesh_terms: D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000737:chemistry*; D001483:Base Sequence; D001665:Binding Sites; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D002151:Calorimetry; D003042:Cocaine / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011803:Quinine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D052157:Aptamers, Nucleotide; D001643:Bridged Bicyclo Compounds; D008024:Ligands; D006859:Hydrogen; D011803:Quinine; D003042:Cocaine
keywords: Aptamer; Calorimetry; ITC; Structure affinity relationship