Small Molecular Weight Compounds Antagonistic to Amyloid Peptide<sub>25-35</sub>

Abstract

High levels of the neurotoxic beta-amyloid protein (Aβ) in patients with Alzheimer's disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator of this condition. Aβ initiates cell receptor and synapse dysfunction, and causes mitochondrial damage within neurons. Neurotransmitters and various small molecular weight compounds ameliorate the effects of Aβ on cell membranes. This study uses a molecular modeling technique to compare the structures of Aβ 25-35 and compounds known to antagonize properties of the polypeptide. Compounds provide good fits to the peptide amino acid residues, revealing planarity in their linear structures and fitting points. Compounds and polypeptide share relative molecular similarity, affinity for receptors and apoptosis modulating properties indicative of their potential for competition at neuron membrane sites. The therapeutic targeting of Aβ by small molecular weight compounds may benefit from a multi-drug approach.