Interactions between the argininyl moieties of neurotensin and the catechol protons of dopamine.
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 x 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 catecholate 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 approximately 10(5) 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.
Schenk
J O
JO
Department of Chemistry, Washington State University, Pullman 99164-4630.
Morocco
M T
MT
Ziemba
V A
VA
D000595:Amino Acid Sequence; D001120:Arginine; D001665:Binding Sites; D002396:Catechols / Q000737:chemistry; D004298:Dopamine / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008433:Mathematics; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011522:Protons; D013053:Spectrophotometry
D002396:Catechols; D011522:Protons; D009496:Neurotensin; D001120:Arginine; C034221:catechol; D004298:Dopamine