کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5216528 | 1383267 | 2014 | 6 صفحه PDF | دانلود رایگان |
Protein misfolding and aggregation are the hallmarks of many devastating diseases. We have previously shown that cyclic d,l-α-peptide CP-2 reacts and stabilizes less toxic forms of amyloid β (Aβ), and protects the cells from Aβ-induced toxicity. Here, we performed extensive structure-based studies on CP-2 to elucidate the contribution of each residue to the total antiamyloidogenic activity and determine the interactions that are involved between CP-2 and Aβ. We showed that the hydrophobicity of CP-2 analogs correlates with their antiamyloidogenic potency, however, aromatic interactions are even more important for this activity. The antiamyloidogenic activity of CP-2 analogs also correlates with their ability to self-assemble, as shown by the critical micelle concentration measurements. The cell survival studies performed on rat pheochromocytoma PC-12 cells suggest that incorporation of an additional aromatic residue to the CP-2's sequence increases its protective effect against Aβ42-induced toxicity.
Journal: Tetrahedron - Volume 70, Issue 42, 21 October 2014, Pages 7639-7644