Structure–affinity relationship of the cocaine-binding aptamer with quinine derivatives. Issue 10 (15th May 2015)

• Record Type: Journal Article
• Authors: Slavkovic, Sladjana; Altunisik, Merve; Reinstein, Oren; Johnson, Philip E.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 10(2015)
• Page Start: 2593
• Page End: 2597
• Publication Date: 2015-05-15
• Subjects: DMSO dimethyl sulfoxide -- ITC isothermal titration calorimetry -- SELEX systematic evolution of ligands by exponential enrichment -- TRIS 2-amino-2-hydroxymethyl-propane-1, 3-diol; Aptamer -- Structure affinity relationship -- ITC -- Calorimetry; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.02.052
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.