Modelagem computacional da glutationa na forma reduzida e oxidada contendo calcogênios selênio e telúrio

Abstract

The present study is aimed to carry out computerized modeling of Glutatione. Glutatione is a tri-peptide composed from the amino acids L-cysteine, L-glutamic acid and glycine. This is a major antioxidant acting as a free radical scavenger that protects the cell from reactive oxygen species (ROS). In addition, GSH is involved in nutrient metabolism and regulation of cellular metabolic functions, ranging from DNA and protein synthesis to signal transduction, cell proliferation, and apoptosis. This complex network of roles, functions, and effects makes GSH and sulfur amino acids a fascinating subject for protein chemists, biochemists, nutritionists, and pathologists. Under normal conditions, glutathione is predominantly present in its reduced form (GSH), with only a small proportion present in its fully oxidised state (GSSG). Motivated by the potential utility of selenium and tellurium against a number of diseases and pathological conditions, we have undertaken this study in order to fill the gap in structural characteristics of the two substituted tri-peptides. The purpose of this dissertation is to perform their structural simulations using the modern molecular modeling software to elucidate the similarities and differences between the substituted derivatives and natural glutathione. The comparative structural modeling of reduced and oxidized glutathiones, as well as their derivatives containing selenium and tellurium in chalcogen sites (Ch = Se, Te) has provided detailed information about the bond lengths and bond angles, filling the gap in the structural characteristics of these tri-peptides. The investigation using the molecular mechanics technique with good approximation confirmed the available information on X-ray refinements for the related compounds. It was shown that Ch-H and Ch-C bond lengths grow in parallel with the increasing chalcogen ionic radii. Although the distances C-C, C-O, and CN are very similar, the geometry of GChChG glutathiones is richer conformers owing to the possibility of rotation about the bridge Ch-Ch. It is confirmed that the distances Ch-Ch are essentially independent of substituents in most of chalcogen compounds from elemental chalcogens oxydized glutathions. The standard program Hyperchem, with MM+ force field, 7.5 has proved to be an appropriate tool for the structural description of less-common bioactive compositions when direct X-ray data are missing.