Small Molecular Weight Compounds Antagonistic to Amyloid Peptide_25-35  

作　　者：W. Robert Williams W. Robert Williams(Faculty of Life Sciences & Education, University of South Wales, Cardiff, UK)

机构地区：[1]Faculty of Life Sciences & Education, University of South Wales, Cardiff, UK

出　　处：《Journal of Biosciences and Medicines》2021年第1期41-51,共11页生物科学与医学（英文）

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.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.

关 键 词：Alzheimer’s Disease Beta-Amyloid Peptide Beta-Amyloid Antagonists Molecular Modeling 

分 类 号：O62[理学—有机化学]