Site-selective protein glycation and PEGylation

A two step protocol has been set up to selectively conjugate PEG to buried amino acids of proteins. The process involves site-specific glycation followed by PEGylation of the oxidized glycosides. Aimed at glycating the cysteine groups of proteins, two maleimide-glycosylic linkers have been synthesised: galactosyl-glucono-CO–NH–(CH₂)₁₂–NH–CO–(CH₂)₂-maleimide and maltosyl-glucono-CO–NH–(CH₂)₁₂–NH–CO–(CH₂)₂-maleimide. The linkers were extensively characterized by ¹H NMR, FT-IR, ESI–TOF mass spectrometry and colorimetric assays. Complete conjugation of the activated linkers to Cys³⁴ of human serum albumin was obtained in about 2 h. The selective oxidation of the galactosyl and maltosyl moieties by periodate treatment yielded two and three available aldehyde groups, respectively. The PEG-hydrazide conjugation to the aldehyde groups was found to be 100% in about 40 h, whereas less than 30% protein modification was obtained by direct conjugation of commercial PEG-maleimide to Cys³⁴. The pH dependent PEG-glycosyl hydrazone bond hydrolysis at various pH values was verified. PEG release was faster under mild acidic and basic conditions than at neutral pH. Furthermore, the maltosyl derivatives, by virtue of the higher number of coupled PEG chains, showed a slower protein release as compared to the galactosyl counterpart, indicating that the choice of the glycosylic linker allows for control of protein release kinetics.     

Maximum likelihood estimation of the Heston stochastic volatility model using asset and option prices: an application of nonlinear filtering theory

Let us suppose that the dynamics of the stock prices and of their stochastic variance is described by the Heston model, that is by a system of two stochastic differential equations with a suitable initial condition. The aim of this paper is to estimate the parameters of the Heston model and one component of the initial condition, that is the initial stochastic variance, from the knowledge of the stock and option prices observed at discrete times. The option prices considered refer to an European call on the stock whose prices are described by the Heston model. The method proposed to solve this problem is based on a filtering technique to construct a likelihood function and on the maximization of the likelihood function obtained. The estimated parameters and initial value component are characterized as being a maximizer of the likelihood function subject to some constraints. The solution of the filtering problem, used to construct the likelihood function, is based on an integral representation of the fundamental solution of the Fokker–Planck equation associated to the Heston model, on the use of the wavelet expansions presented in (Fatone et al. in High performance algorithms based on a new wavelet expansion for time dependent acoustic obstacle scattering. Commun. Computat. Phys. (2007), Research Developments in Acoustics, vol. 2, pp. 39–69. Transworld Research Network, Kerala (2005), New wavelet bases made of piecewise polynomial functions: approximation theory, quadrature rules and applications to kernel sparsification and image compression. SIAM J. Sci. Comput. (submitted)) to approximate the integral kernel appearing in the representation formula of the fundamental solution, on a simple truncation procedure to exploit the sparsifying properties of the wavelet expansions and on the use of the fast Fourier transform (FFT). The use of these techniques generates a very efficient and fully parallelizable numerical procedure to solve the filtering problem, this last fact makes possible to evaluate very efficiently the likelihood function and its gradient. As a byproduct of the solution of the filtering problem we have developed a stochastic variance tracking technique that gives very good results in numerical experiments. The maximum likelihood problem used in the estimation procedure is a low dimensional constrained optimization problem, its solution with ad hoc techniques is justified by the computational cost of evaluating the likelihood function and its gradient. We use parallel computing and a variable metric steepest ascent method to solve the maximum likelihood problem. Some numerical examples of the estimation problem using synthetic and real data, that is data relative to an index of the Milano stock exchange (S&PMIB30), obtained with a parallel implementation of the previous numerical method are presented. Very impressive speed up factors are obtained in the numerical examples using the parallel implementation of the numerical method proposed. The website: http://www.econ.univpm.it/pacelli/mariani/finance/w1 contains animations and some auxiliary material that helps the understanding of this paper and makes available to the interested users the computer programs used to produce the numerical experience presented. The numerical experience reported in this paper has been obtained using the computing grid of ENEA (Rome, Italy). The support and sponsorship of ENEA are gratefully acknowledged.     

Interaction of cisplatin with human superoxide dismutase

cis-Diamminedichloroplatinum(II) (cisplatin) is able to interact with human superoxide dismutase (hSOD1) in the disulfide oxidized apo form with a dissociation constant of 37 ± 3 μM through binding cysteine 111 (Cys111) located at the edge of the subunit interface. It also binds to Cu(2)-Zn(2) and Zn(2)-Zn(2) forms of hSOD1. Cisplatin inhibits aggregation of demetalated oxidized hSOD1, and it is further able to dissolve and monomerize oxidized hSOD1 oligomers in vitro and in cell, thus indicating its potential as a leading compound for amyotrophic lateral sclerosis.     

Heat Transfer Problem in a Van Der Waals Gas

This paper is devoted to the study of a heat transfer problem in a van der Waals gas. We found that the extended thermodynamics theory for such a fluid predicts the non-vanishing dynamic pressure and the shear stress tensor, even in the simplest stationary planar case. However, the order of magnitude of the non-equilibrium variables is very small and, consequently, their experimental observation seems to be quite difficult. A comparison between the results derived from the classical Navier–Stokes Fourier theory and those from extended thermodynamics is also presented.     

Self-assembly of a cavitand-based heteronuclear coordination cage

A new self-assembly protocol leading to the formation of heteronuclear coordination cage 10 is reported. Reaction of tetradentate cavitand ligand 1, bearing one ethynylpyridine and three benzonitriles at the apical positions, with Pt(dppp)OTf₂ and Pd(dppp)OTf₂ in a 1:3 ratio yields 10 as the thermodynamic product. Under the same conditions, the self-assembly of 1 with either Pt or Pd metal precursors gives a mixture of isomeric homonuclear cages 8a-c or 9a-c, respectively.     

First synthesis of 2,6-diazabicyclo[3.2.0]heptane derivatives

The first synthesis of 6-phenyl-2,6-diazabicyclo[3.2.0]heptane 1 and its orthogonally protected precursor 2 is herein reported. Our strategy enables to chemically address the two nitrogen atoms of 2,6-diazabicyclo[3.2.0]heptane core individually and selectively, thus allowing rapid access to several subsets of widely substituted fused azetidines.     

Characterization of 2,5‐diaryl‐1,3,4‐oxadiazolines by multinuclear magnetic resonance and density functional theory calculations. Investigation on a case of very remote Hammett correlation

Two series of 2,5‐diaryl‐1,3,4‐oxadiazolines have been studied by multinuclear magnetic resonance and density functional theory calculations. A full NMR spectroscopic characterization has been performed and excellent remote Hammett correlations (σ_p or ) have been found for para substitution in the two aryl rings through at least 11 bonds, notwithstanding the presence in the path of atoms that should act as insulators and a lack of correlation for some of the intermediate atoms. The computational investigation on the electronic delocalization, performed with the ACID (anisotropy of the induced current density) method, reveals indeed that electrons are delocalized in almost the entire molecule despite the presence of the insulators. Copyright © 2009 John Wiley & Sons, Ltd.