Abstract
The interaction of the antidepressant drug imipramine with insulin in aqueous solution at pH = 3.2(ionic strength Ic= 6.5 · 10−3mol · dm−3) has been investigated by equilibrium dialysis and microcalorimetry. Imipramine binds to insulin to the extent of ≈ (50to 60) imipramine molecules per insulin molecule in the temperature range T= (283.15 to 308.15) K. The binding data have been used to obtain the Gibbs energy per imipramine molecule boundΔGν using the Wyman binding potential approach. The enthalpy of the interaction is small and exothermic following a sigmoidal curve as a function of binding, andΔGν is dominated by a large entropy increase on binding which is of similar magnitude to the non-specific hydrophobic binding of several other amphipathic ligands with globular proteins.
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