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Light-controlled molecular tweezers capture specific amyloid oligomers
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  • Chengyuan Qian,
  • Jiefang Chen,
  • Cheng Wang,
  • Qiang Wang,
  • Xiaoyong Wang,
  • Xiaohui Wang
Chengyuan Qian
Nanjing Tech University
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Jiefang Chen
Nanjing Tech University
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Cheng Wang
Nanjing Tech University
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Qiang Wang
Nanjing Tech University
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Xiaoyong Wang
Nanjing University
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Xiaohui Wang
Nanjing Tech University

Corresponding Author:[email protected]

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Abstract

Amyloid-β peptide (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 specifc 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 (C. elegans) in vivo under light irradiation. The LMTs may serve as spatiotemporally controllable molecular tools to extract specific native oligomers for the structure and function studies via their reversible photoisomerization, which would improve the understanding of the toxic mechanisms of Aβ oligomers and development of oligomer-targeted diagnosis and therapy.
20 Sep 2023Submitted to Aggregate
25 Sep 2023Submission Checks Completed
25 Sep 2023Assigned to Editor
26 Sep 2023Reviewer(s) Assigned
04 Oct 2023Review(s) Completed, Editorial Evaluation Pending
05 Oct 2023Editorial Decision: Revise Major
31 Oct 20231st Revision Received
31 Oct 2023Submission Checks Completed
31 Oct 2023Assigned to Editor
01 Nov 2023Reviewer(s) Assigned
02 Nov 2023Review(s) Completed, Editorial Evaluation Pending
03 Nov 2023Editorial Decision: Accept