Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation

Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions ; (2) to elucidate the molecular basis of their biological effects ; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation

Selenocysteine derivatives I. Sidechain conformational potential energy surface of N-acetyl-L-selenocysteine-N-methylamide (MeCO-L-Sec-NH-Me) in its beta(L) backbone conformation

Selenocysteine is expected to have 92=81 conformations [in the backbone: y(g+,a,g-)¥f(g+,a,g-); 32=9 and in the sidechain: c1(g+,a,g-)¥c2(g+,a,g-); 32=9]. All torsional modes of the sidechain (c1: rotation about the Ca–Cb and c2: rotation about the Cb–Se bonds) were investigated in the relaxed bl backbone [(y,f), (a,a)] conformation. The relaxed potential energy surface (PES) obtained at the RHF/3-21G level of theory contained seven out of nine possible minima of the sidechain. All minima were re-optimized at the RHF/6-31G(d) and the B3LYP/6-31G(d) levels of theory. Two of the minima (g+a) and (g-g+) located at RHF/3-21G level of theory were annihilated when optimized at higher levels of theory. The frequency calculations for the found minima were used to construct the thermodynamic functions. The relative energies of the –CH2–SeH sidechain conformations have been compared with the relative energies of the analogous –CH2–SH and –CH2–OH sidechain conformers. Oxidative dimerization energies were also estimated