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Amorphous Protein Aggregation Detected by Rational Designed Fluorescent Probes
  English.dicp.cas.cn    Posted:2021-06-08    From:Group 02T5

Most current protein aggregation sensors focus on amyloid proteins for their well-defined β-sheet stacked structure. Intracellular amorphous protein aggregation with random and indefinite structure is usually envisioned to be untargetable or undruggable by small molecule probes.

Recently, Prof. LIU Yu's group and Prof. PIAO Hailong's group from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Science (CAS), in collaboration with Prof. LIU Xiaojing from Shandong University, rationally designed amorphous protein aggregation sensors from aggregation induced emission probes (AIEgens), and systematically investigated the structure-fluorescence relationship to dissect structural moieties.

This study was published in Angewandte Chemie International Edition on May 14.


Rational design of crystallization induced emission probes to detect amorphous protein aggregation in live cells (Image by SHEN Di)

The researchers used photo-physical measurements, biophysical analyses, and theoretical calculation to identify key structural elements for an AIEgen. And finally they acquired three satisfactory properties.

First, Dimethylaminophenylene that up-regulated polarity and viscosity sensitivity was the essential moiety to recognize amorphous aggregates and turn on the fluorescence. Second, Electron withdrawing moieties fine-tuned the emission wavelength; Last but not the least, Balancing probe's lipophilicity and solubility contributed to the cellular signal-to-noise ratio.

They further demonstrated these features were generally applicable to other AIEgens.

"This work may provide a new strategy for further design of imaging sensors, proteomics probes, and therapeutic reagents for amorphous aggregated protein," said Prof. LIU.

This work was supported by the National Natural Science Foundation of China, Liaoning Revitalization Talents Program, China Postdoctoral Science Foundation Grant, and Dalian Innovation Fund. (Text by SHEN Di)

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