Interactions Between the Argininyl Moieties of Neurotensin and the Catechol Protons of Dopamine

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Abstract
: The interaction between dopamine and neurotensin as well as other Arg‐containing peptides was studied to provide more chemical details of how dopamine binds to the neuropeptide neurotensin. The stoichiometry of 1:1, dopamine to neurotensin, was confirmed by additional electroanalytical and ultraviolet‐visible spectroscopic studies. By analyses of the 205‐to 340‐nm difference spectra of fixed concentrations of dopamine in the presence of increasing amounts of neurotensin, the dissociation constant of the interaction was found to be 5.9 × 10−8 mol/L. This finding confirmed (by a second physical method) the previously reported KD value obtained by electroanalytical techniques. The associations between dopamine and neurotensin as well as the neurotensin fragment Pro7‐Arg8‐Arg9‐Pro10 were found to be pH dependent when the dissociation constant was measured as a function of pH (in 150 mmol/L NaCl). The results of studies of the formal potential of dopamine in the presence of Arg and Arg‐containing peptides confirmed that catechol protons are directly involved in the association and that the chemical species of dopamine associated with neurotensin is a cate‐cholate form. The (pseudo)‐first‐order rate constant of dissociation of the complex at pH 7.6, measured by the chronoamperometric and rotating disk electroanalytical techniques, was found to be ⋍105 s−1, indicating that the rate of formation of the complex is under diffusion control. A hypothetical chemical structure of the neurotensin‐dopamine complex is suggested.