Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research , Sector 67, S.A.S Nagar 160 062, Punjab India.
Department of Microbial Biotechnology, Panjab University , Sector 14, Chandigarh 160 014, India.
ACS Chem Neurosci. 2016 May 18;7(5):615-23. doi: 10.1021/acschemneuro.6b00006. Epub 2016 Feb 16.
Amyloid-β aggregation is a major etiological phenomenon in Alzheimer's disease. Herein, we report peptide-based inhibitors that diminish the amyloid load by obviating Aβ aggregation. Taking the hexapeptide fragment, Aβ32-37, as lead, more than 40 new peptides were synthesized. Upon evaluation of the newly synthesized hexapeptides as inhibitors of Aβ toxicity by the MTT-based cell viability assay, a number of peptides exhibited significant Aβ aggregation inhibitory activity at sub-micromolar concentration range. A hexapeptide (1) showed complete mitigation of Aβ toxicity in the cell culture assay at 2 μM. In the ThT fluorescence assay, upon incubation of Aβ with this peptide, we observed no increase in the ThT fluorescence relative to control. The secondary structure estimation by circular dichroism spectroscopy and morphological examination by transmission electron microscopy further confirmed the results.
淀粉样蛋白-β聚集是阿尔茨海默病的主要病因现象。在此，我们报告了基于肽的抑制剂，通过避免 Aβ聚集来减少淀粉样蛋白负荷。以六肽片段 Aβ32-37 为先导，合成了 40 多个新肽。通过 MTT 基础细胞活力测定评估新合成的六肽作为 Aβ毒性抑制剂，一些肽在亚微摩尔浓度范围内表现出显著的 Aβ聚集抑制活性。一种六肽（1）在 2μM 时在细胞培养测定中完全减轻了 Aβ的毒性。在 ThT 荧光测定中，当将 Aβ与该肽孵育时，与对照相比，未观察到 ThT 荧光增加。圆二色性光谱的二级结构估算和透射电子显微镜的形态检查进一步证实了这一结果。
