Estudo computacional das propriedades miméticas de peptídeos usados como potenciais atenuantes da interação metal-proteína no combate à doença de alzheimer

Abstract

Alzheimer's disease is a complex neurodegenerative condition characterized by a series of pathological events in the brain, such as the dysregulation of metal homeostasis. There is evidence that metal ions interact with the Aβ protein, forming neurotoxic oligomeric species, especially in the case of Cu(II) ions, which can promote the generation of reactive oxygen species. In this context, the development of compounds capable of attenuating the interaction between metals and the Aβ protein (MPACs) emerges as a promising approach, as these agents prevent the formation of the toxic complex while maintaining the availability of metals for essential biological functions. The use of peptide structures as potential drugs has also gained prominence. This study evaluated five synthetic decapeptides, investigating their ability to attenuate the interaction between metals and the Aβ protein. The cyclic structures demonstrated greater conformational stability compared to the linear ones, with the sequence containing aspartate standing out by presenting the best results. The structure with D-proline did not show significant conformational differences compared to L-proline. The presence of the metal contributed to greater conformational stability of the C-Asp ligand. Nevertheless, this ligand does not interact significantly with the Aβ(1-16) protein. This work provides a relevant computational contribution for future investigations.