Interaction of Cisplatin with a CCHC Zinc Finger Motif

The interaction between cisplatin and an 18-residue CCHC zinc finger motif derived from a retroviral nucleocapsid protein (PyrZf18) has been studied using UV–visible, CD and 1H NMR spectroscopies and ESI-MS spectrometry. Cisplatin irreversibly blocks the cysteine zinc binding groups in the free peptide and is able to slowly eject zinc from the zinc–peptide complex. The observed end product of the reaction with cisplatin is a complex in which only one ammonia molecule is coordinated to platinum. After an initial binding with two cysteine residues and the formation of the (PyrZf18)– platinum–(NH3)2 complex, a release of one ammonia molecule occurs because of trans-labilization, and the third cysteine is coordinated, leading to a mixture of isomers and/or conformers of the (PyrZf18)–platinum–NH3 complex. The results are discussed with respect to the potential antiretroviral activity of platinum(II) compounds and to the possible interaction of cisplatin with the cellular nucleic acid binding proteins

Corporate governance for sustainability : Statement

The current model of corporate governance needs reform. There is mounting evidence that the practices of shareholder primacy drive company directors and executives to adopt the same short time horizon as financial markets. Pressure to meet the demands of the financial markets drives stock buybacks, excessive dividends and a failure to invest in productive capabilities. The result is a ‘tragedy of the horizon’, with corporations and their shareholders failing to consider environmental, social or even their own, long-term, economic sustainability. With less than a decade left to address the threat of climate change, and with consensus emerging that businesses need to be held accountable for their contribution, it is time to act and reform corporate governance in the EU. The statement puts forward specific recommendations to clarify the obligations of company boards and directors and make corporate governance practice significantly more sustainable and focused on the long term

Corporate Governance for Sustainability

The current model of corporate governance needs reform. There is mounting evidence that the practices of shareholder primacy drive company directors and executives to adopt the same short time horizon as financial markets. Pressure to meet the demands of the financial markets drives stock buybacks, excessive dividends and a failure to invest in productive capabilities. The result is a ‘tragedy of the horizon’, with corporations and their shareholders failing to consider environmental, social or even their own, long-term, economic sustainability. With less than a decade left to address the threat of climate change, and with consensus emerging that businesses need to be held accountable for their contribution, it is time to act and reform corporate governance in the EU. The statement puts forward specific recommendations to clarify the obligations of company boards and directors and make corporate governance practice significantly more sustainable and focused on the long term

Tumor Necrosis Factor-a Neutralizing Antibodies Induced by a Glycolaldehyde-Modified C- terminal Polypeptide.

TNF-a is a pro-inflammatory cytokine that is overexpressed in diverse inflammatory states such as rheumatoid arthritis. Anti-TNF therapies, including monoclonal antibodies (Abs), have demonstrated remarkable success in management of arthritis and other chronic inflammatory diseases. The possibility to elicit autoAbs to TNF-a (beneficial autoimmunity) has been proposed as an immunotherapeutic approach to neutralize systemic TNF-a (1). Studies using a DNA vaccination strategy in rat adjuvant arthritis mapped several epitopes for natural anti-TNF-a autoAbs in the C-terminal portion of the sequence. We previously showed that aldehyde-tagged peptide conjugates representing immunogenic epitopes of toxic shock syndrome toxin–1, could induce anti-toxin neutralizing Abs without the need of potent adjuvants (2). In the present study, using a C-terminal TNF-a recombinant polypeptide, we followed a similar approach to generate neutralizing Abs against TNF-a in Lewis rats. Immunized rats showed less severe symptoms in the collagen induced arthritis ( CIA) model. 1. Dalum I. et. al. Therapeutic antibodies elicited by immunization against TNF-alpha. Nat Biotechnol 1999. 17:666-669. 2. Bavoso A, Ostuni A, De Vendel J, Pollaro F, Armentano F, Knight T, Makker S. and A. Tramontano. Aldehyde modification of peptide immunogen enhances protein-reactive antibody response to toxic shock syndrome toxin-1. J Pept Sci 2006. 12:843-849

Investigation on coordination ability of N-chloro-acetylglycine towards Cu(II) in solid and solution state

The solution and solid state behavior of the binary system Cu(II)-N-chloroacetylglycine (Cl-acglyH) and the corresponding ternary systems with 2,2\ub4-bipyridine (bpy) and 1,10-phenanthroline (ophen) were investigated by means of pH-metric and spectrophotometric titrations. The X-ray crystal structure of the complex [Cu(ophen)(Cl-acgly)(2)]..2H2(O) (Cl-acgly=N-chloroacetylglycine monoanion) is also reported. The crystals of the compound C20Cl2CuN4O8H22 are monoclinic, space group P2(1)/c, a=17.574(3), b=7.125(2), c=25.113(6) Angstrom, beta=130.04(2)degrees, Z=4, R=0.077, R-w=0.088. The structure consists of monomeric [Cu(ophen)(Clgly)(2)] units and lattice water molecules. The Cu(II) atom is square planar coordinated by two carboxylic oxygens of two amino acid molecules and two nitrogen atoms of the ophen molecule. Two long contacts involve the uncoordinated carboxylic oxygens. Crystal packing is due to ring-stacking interaction involving ophen molecules and to a strong intramolecular hydrogen bond involving the chlorine atom and the amidic nitrogen of one ligand molecule. In solution the species [CuI2] and [CuALOH] (A = bpy or ophen) prevail in the binary and ternary system, respectively, both arising from carboxylic-oxygen-metal coordination of the amino acid molecule. The coordination of the OH- group in the ternary species prevents metal hydrolysis up to pH 11. The possibility of forming hydrogen bond interactions involving the chlorine atom seems the to be determinant factor in stabilizing the ternary complexes