Development of novel small-size peptides as putative therapeutic drugs

Abstract

This thesis focuses on the development of small peptide molecules with either antifungal properties or with the ability to control protein deposits that cause the characteristic brain damage in Alzheimer's disease (AD). Thus, our ultimate aim is to design putative therapeutic agents supported by computational techniques. Apropos of AD, this is a very complex disease where brain damage is associated with the degradation of the human mind and memory. Currently, researchers consent that a key role is played by a peptide called beta-amyloid. This peptide is not toxic by itself, however it becomes toxic to nerve-cells when several of its molecules clump together forming aggregates. This is the beginning of a slow but unstoppable brain deterioration, which ultimately leads to dementia. The currently available AD drugs delay, at best, the loss of memory, but do not stop the neural degradation. Its severity and the increasing number of AD patients, are the worldwide driving force to acquire more effective drugs. In our own research we focused on the development of new peptides that prevent or slow down the formation of the aggregated beta-amyloid. Computational techniques allowed us to explore the self-bound beta-amyloid molecules, as well as their interaction with new potential drugs. With this fascinating information we designed small peptides aimed at disrupting the aggregated beta-amyloid. Then, its anti-amyloid activity of was tested in vitro and in vivo. Both tests have produced not only positive but also striking and promising results indicating the potential therapeutic application of these new anti-amyloid peptides.