title: Studies of the mechanism of chloroquine binding to synthetic DOPA-melanin.
abstract: In order to elucidate the mechanism of drugs binding to melanin, effects of pH, ionic strength and organic solvent on the interaction of chloroquine with synthetic dopa-melanin were studied. The results indicate that electrostatic, hydrophobic and van der Waals' forces participate in the formation of the chloroquine-melanin complex. Binding analysis by the Scatchard method showed that two classes of binding sites take part in the complex formation: strong binding sites with the association constant k1 approximately to 10(5) and weak binding sites with K2 approximately 10(4). Experiments with chemically modified melanin yielded some information about binding sites of this biopolymer. The obtained results suggest that strong binding involves both hydrophobic interaction and electrostatic attraction between the protonated ring system of chloroquine and the ortho-semiquinone groups of melanin. However, the weakly reacting sites can be identified as ionic bonds between protonated aliphatic nitrogen of chloroquine molecule and carboxyl groups of melanin. Van der Waals' forces occurring at the conjunctions of the aromatic rings of the drug and the aromatic indole-nuclei of the melanin probably take part in the weak binding too.
mesh_terms: D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D002738:Chloroquine; D004295:Dihydroxyphenylalanine; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008543:Melanins; D009994:Osmolar Concentration; D012965:Sodium Chloride
chemical_list: D008543:Melanins; D012965:Sodium Chloride; D004295:Dihydroxyphenylalanine; D002738:Chloroquine