Binding of Oxovanadium(IV) to Tripeptides Containing Histidine and Cysteine Residues and Its Biological Implication in the Transport of Vanadium and Insulin‐Mimetic Compounds

Abstract

The complexation of VIVO ion with three tripeptides of biological importance containing L‐histidine or L‐cysteine (HisGlyGly, GlyGlyHis and GlyGlyCys) has been studied. This study was performed in aqueous solution by the combined application of potentiometric and spectroscopic (electronic absorption and EPR) techniques. The results indicate that these oligopeptides, if a ligand‐to‐metal molar ratio of 10 or 15 is used, can keep VIVO ion in solution until the deprotonation of the amide group with the donor set (NH2, CO, Nimax) for HisGlyGly or (COO–, CO) for GlyGlyHis and GlyGlyCys. In all the systems, at pH values around neutrality, a VOLH–2 species is formed with an (NH2, N–, N–, COO–) donor set for HisGlyGly, (NH2, N–, N–, Nim) for GlyGlyHis and (NH2, N–,N–, S–) for GlyGlyCys. These species, and those with onedeprotonated amide group coordinated to the VIVO ion, can be detected by EPR spectroscopy. The N–(amide) contribution to the hyperfine coupling constant along the z axis, Az, depends on the total charge of the donor atoms in the equatorial plane. The participation of albumin in the transport of vanadium and insulin‐mimetic VIVO compounds is reconsidered based on these results. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Interaction of VO2+ ion with human serum transferrin and albumin

“…What is sure is that the donors of albumin are stronger than those of transferrin (A z = 165 Â 10 À4 cm À1 for HSA vs. A z = 168 À 172 Â 10 À4 cm À1 for hTf) and that VO 2+ ion, differently from Cu 2+ and Ni 2+ , does not interact with the N-terminal part of albumin, as previously proposed [10,27]. In fact, the donor set (NH 2 , N À , N À , N imid ) gives a value of A z (151 Â 10 À4 cm À1 ), sensibly lower than that measured for HSA [65].…”

Unveiling VIVO2+ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

“…For this binding mode, the “additivity relationship”, suggests that | A z | estmtd is 151.4×10 −4 cm −1 , very far from the values observed for HSA d , which are in the range (163–169)×10 −4 cm −1 (see above). Moreover, to induce the deprotonation of amide nitrogen atoms in the tripeptide GlyGlyHis and reveal the (NH 2 , N − , N − , His‐N) coordination, a ligand‐to‐metal molar ratio of 15:1 must be used and this mode can be clearly detected only at pH>7.5 . Similar findings were also reached by other authors …”

“…It is noteworthy that V IV O 2+ , in contrast with Cu 2+ and Ni 2+ ions, does not interact with the ATCUN motif as the donor set (Asp1‐NH 2 , N − , N − , His3‐N), where N − denotes the deprotonated amide groups of residues 2 and 3, should give spin Hamiltonian parameters significantly different from the experimental ones for HSA ( g z =1.960 and A z =153×10 −4 cm −1 were measured in the model system V IV O 2+ ‐GlyGlyHis for (NH 2 , N − , N − , His‐N) coordination). For this binding mode, the “additivity relationship”, suggests that | A z | estmtd is 151.4×10 −4 cm −1 , very far from the values observed for HSA d , which are in the range (163–169)×10 −4 cm −1 (see above).…”

Comparative Study of the Reactivity of Zirconium(IV)‐Substituted Polyoxometalates towards the Hydrolysis of Oligopeptides

“…In addition to these expected shifts for the acceleration of the hydrolysis of the peptide bonds in GGH, similar shifts of the resonances of all other carbon atoms to those observed in the presence of 1 were also obtained in the presence of 2 and 3 . These results demonstrate multiple coordination modes for the complexation of Zr IV ‐substituted POMs to GGH, similarly to the multiple coordination modes that were observed between oxovanadium and this tripeptide 17…”