Heng Liu, Yunpeng Cui, Xue Zhao, Lulu Wei, Xudong Wang, Ning Shen, Timothy Odom, Xuming Li, William Lawless, Kanchana Karunarathne, Martin Muschol, Wayne Guida, Chuanhai Cao, Libin Ye, Jianfeng Cai
In contrast to prevalent strategies which make use of β-sheet mimetics to block Aβ fibrillar growth, in this study, we designed a series of sulfonyl-γ-AApeptide helices that targeted the crucial α-helix domain of Aβ13-26 and stabilized Aβ conformation to avoid forming the neurotoxic Aβ oligomeric β-sheets. Biophysical assays such as amyloid kinetics and TEM demonstrated that the Aβ oligomerization and fibrillation could be greatly prevented and even reversed in the presence of sulfonyl-γ-AApeptides in a sequence-specific and dose-dependent manner...
February 6, 2024: Proceedings of the National Academy of Sciences of the United States of America