Interaction of VO2+ Ion and Some Insulin-Enhancing Compounds with Immunoglobulin G.

Complexation of VO2+ ion with the most abundant class of human immunoglobulins, immunoglobulin G (IgG), was studied using EPR spectroscopy. Differently from the data in the literature which report no interaction of IgG with vanadium, in the binary system VO2+/IgG at least three sites with comparable strength were revealed. These sites, named 1, 2, and 3, seem to be not specific, and the most probable candidates for metal ion coordination are histidine-N, aspartate-O or glutamate-O, and serinate-O or threoninate-O. The mean value for the association constant of (VO)xIgG, with x = 3-4, is log ? = 10.3 ± 1.0. Examination of the ternary systems formed by VO2+ with IgG and human serum transferrin (hTf) and human serum albumin (HSA) allows one to find that the order of complexing strength is hTf >> HSA ? IgG. The behavior of the ternary systems with IgG and one insulin-enhancing agent, like [VO(6-mepic)2], cis-[VO(pic)2(H2O)], [VO(acac)2], and [VO(dhp)2], where 6-mepic, pic, acac, and dhp indicate the deprotonated forms of 6-methylpicolinic and picolinic acids, acetylacetone, and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, is very similar to the corresponding systems with albumin. In particular, at the physiological pH value, VO(6-mepic)(IgG)(OH), cis-VO(pic)2(IgG), and cis-VO(dhp)2(IgG) are formed. In such species, IgG coordinates nonspecifically VO2+ through an imidazole-N belonging to a histidine residue exposed on the protein surface. For cis-VO(dhp)2(IgG), log ? is 25.6 ± 0.6, comparable with that of the analogous species cis-VO(dhp)2(HSA) and cis-VO(dhp)2(hTf). Finally, with these new values of log ?, the predicted percent distribution of an insulin-enhancing VO2+ agent between the high molecular mass (hTf, HSA, and IgG) and low molecular mass (lactate) components of the blood serum at physiological conditions is calculated.