Massimiliano Francesco Peana

Multidimensional NMR spectroscopy for the study of histone H4–Ni(II) interaction

The N-terminal 30-amino acid tail of histone H4, a nuclear protein, was studied as a model for the interaction of this protein with Ni(ii) ions. The behaviour of the ends-blocked Ac-SGRGKGGKGLGKGGA(15)K(16)R(17)H(18)R(19)KVLRDNIQGIT-Am fragment towards Ni(ii) was analyzed with multidimensional NMR (1D, 2D TOCSY, NOESY) and UV-Vis spectroscopy. As expected, the coordination involved the imidazolic nitrogen of the His(18) residue and the three deprotonated amidic nitrogens of the His(18), Arg(17) and Lys(16) residues, respectively. A model for the structure of the complex was calculated from the inter-residual NOEs recorded in 2D NOESY spectra. The structure obtained shows that the interaction with the metal is responsible for deep changes in the conformation of the peptide, blocking the side chain of Arg(17) and Lys(16) residues above the coordination plane. These structural modifications may be physiologically relevant to the mechanism of nickel carcinogenesis.

Nutritional iron deficiency: the role of oral iron supplementation

Nutritional iron deficiency represents a relevant health problem mainly in developing countries. Children and pregnant women represent the main target of this disease, and the low amount of bio-available iron mostly depends on plant-based diets. Iron deficiency may have serious consequences, with severe impairment of the immune function leading to infectious diseases. The brain development in embryos and fetuses during gestation can be greatly affected by iron deficiency of the mother with heavy outcomes on the cognition status of children. A better understanding of molecular pathways involved in iron absorption and metabolism are the basis for new strategies for developing a therapy for iron deficiency. Different therapeutic strategies are summarized, and iron fortification appears the best tool.

Warns against unapproved ‘chelation therapy’

At Eurobic11 in Granada we presented a Keynote Lecture on chelation therapy, a consolidated medical procedure used primarily to hinder the effects of toxic metal ions on human tissues. Its application spans a broad spectrum of serious disorders, ranging from acute metal intoxication to genetic metal-overload. The use of chelating agents is compromised by a number of serious side effects, mainly attributable to perturbed equilibrium of essential metal ion homeostasis and dislocation of complexed metal ions to dangerous body sites. For this reason, chelation therapy has been limited to specific critical and otherwise untreatable conditions and it needs to be monitored within an appropriate clinical context. In this meeting we want warn against the widespread fraudulent use of the term ‘‘chelation therapy’’ to take advantage of and make profit from people with tragic health problems. We believe that scientists working in this field have the corollary obligation to deter these frauds and to inform the scientific community of the possible side effects and complications of chelation therapy. This duty is all the more important if we consider the detrimental and even life threatening consequences that can occur in subjects with no clear clinical and laboratory evidence of metal intoxication. The aim of this communication is to present how this ‘‘false chelation therapy’’ developed and in which diseases it is currently applied. This research was supported by the Regione Autonoma Sardegna [CRP-27564].AW 1 Vanadium: its role in life and environmental issues Dieter Rehder Department of Chemistry, University of Hamburg, Martin-LutherKing-Platz 6, 20146 Hamburg, Germany. rehder@chemie.unihamburg.de Vanadium is the second-to-most abundant transition metal in sea water. Marine macroalgae employ vanadate, built into the active centre of vanadate-dependent haloperoxidases VHPOs, in the peroxidation of halides (Hal) to Hal species. Hal can generate halomethanes that are released into the atmosphere [1] where they are involved in ozone depletion; see Figure. VHPOs are also present in some terrestrial fungi, in lichen and in Streptomyces bacteria. The biocidal (antifouling) and oxidative power of VHPOs have initiated research into applications, including active centre models, in medicinal (disinfection) and industrial (oxidation catalysis) fields [2]. In the context of possible medicinal applications of vanadium compounds it is worth noting that vanadate HVO4 2is an antagonist of phosphate: Vanadate appears to have a cardioand neuro-protective potential, and oxidovanadium(IV) and –(V) chelates have been show to exert in vitro and in vivo anti-cancer, anti-viral and anti-bacterial activity [3]. The most prominent issue in a medicinal context is the insulinenhancing action of vanadyl chelates such as VO(acac)2 and VO(maltol)2. Vanadium can enter the cytosol directly as vanadate, or in the form of VO coordinated to transferrin and serum albumin. Its possible primary mode of action is the regulation of the tyrosine phosphorylation level of the insulin receptor (and thus the glucose signalling path) by interacting with protein tyrosine phosphatase 1B [2, 3].