Light-controlled molecular tweezers capture specific amyloid oligomers  

作　　者：Chengyuan Qian Jiefang Chen ChengWang QiangWang Xiaoyong Wang Xiaohui Wang 

机构地区：[1]Institute of Chemical Biology and Functional Molecules,State Key Laboratory of Materials-Oriented Chemical Engineering,School of Chemistry and Molecular Engineering,Nanjing Tech University,Nanjing,P.R.China [2]State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University,Nanjing,P.R.China

出　　处：《Aggregate》2024年第2期378-385,共8页聚集体（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Numbers:21771105,22377053;Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20170103;The Six Talent Peaks Project in Jiangsu Province,Grant/Award Number:SWYY-043。

摘　　要：Amyloid-βpeptide(Aβ)oligomers,characteristic symptom of Alzheimer’s disease(AD),have been identified as the most neurotoxic species and significant contributors to neurodegeneration in AD.However,due to their transient and heterogeneous nature,the high-resolution structures and exact pathogenic processes of Aβ oligomers are currently unknown.Using light-controlled molecular tweezers(LMTs),we describe a method for precisely capturing specific Aβ oligomers produced from synthetic Aβ and AD animal models.Light irradiation can activate LMTs,which are composed of two Aβ-targeting pentapeptides(KLVFF)motifs and a rigid azobenzene(azo)derivative,to form a tweezer-like cis configuration that preferentially binds to specific oligomers matching the space of the tweezers via multivalent interactions of KLVFF motifs with the oligomers.Surprisingly,cis-LMTs can immobilize the captured oligomers in transgenic Caenorhabditis elegans under light irradiation.The LMTs may serve as spatiotemporally controllable molecular tools to extract specific native oligomers for the structure and function studies via reversible photoisomerization,which would improve the understanding of the toxic mechanisms of Aβoligomers and development of oligomer-targeted diagnosis and therapy.

关 键 词：Alzheimer’s disease amyloid oligomers molecular tweezers PHOTOISOMERIZATION precise capture 

分 类 号：O63[理学—高分子化学]