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

• 作者: W. Robert Williams
• 来源期刊: 生物科学与医学(英文)
• 学科: 化学
• 关键词: Alzheimer’s Disease Beta-Amyloid Peptide Beta-Amyloid Antagonists Molecular Modeling
• 年，卷（期）: 2021,（1）
• 页码范围: 41-51
• 页数: 11页
• 分类号: O62

摘要

High levels of the neurotoxic beta-amyloid protein (A<em>β</em>) in patients with Alzheimer’s disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator of this condition. A<em>β</em> initiates cell receptor and synapse dysfunction, and causes mitochondrial damage within neurons. Neurotransmitters and various small molecular weight compounds ameliorate the effects of A<em>β</em> on cell membranes. This study uses a molecular modeling technique to compare the structures of A<em>β</em>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 A<em>β</em> by small molecular weight compounds may benefit from a multi-drug approach.