A Light-Up Strategy with Aggregation-Induced Emission for Identification of HIV-I RNA-Binding Small Molecules

Fluorescence methods are important tools to identify RNA-binding small molecules and further employed to study RNA-protein interactions. Most reported fluorescence strategies are based on covalent labeling of ligand or RNA, which can impede the binding between them to some extent, or light-off fluorescent indicator displacement methods, which ask for particular indicators. Herein, a label-free fluorescence strategy based on the light-on aggregation-induced emission (AIE) feature of tetraphenylethene (TPE) derivative to screen RNA-binding small molecules is presented. As a result of electrostatic interaction, the selected peptides can induce self-assembly of the TPE derivative to produce strong fluorescent emission; when the peptides are bound to RNA molecules, the TPE derivative is in the deaggregated form and shows no or minimum fluorescence. Based on the phenomenon, a competitive displacement assay combined with the TPE reporter was employed to characterize selected small molecules for their binding abilities to HIV-I RNAs. This AIE feature enables the fluorescence-off state of the TPE derivative in the presence of RNA-peptide complex to be "lightened up" quickly as the RNA-binding molecule is introduced and the peptide is competitively released. This strategy was carried out to test several small molecule binders, and the results are consistent with previous reports. This report gives an inspiring example of AIE-based fluorescent assay for HIV-I RNA-binding molecule screening, which may further be explored to build a drug screening platform for RNA-protein interference.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:92

Enthalten in:

Analytical chemistry - 92(2020), 19 vom: 06. Okt., Seite 13532-13538

Sprache:

Englisch

Beteiligte Personen:

Li, Jun [VerfasserIn]
Fan, Yao-Yao [VerfasserIn]
Wang, Man [VerfasserIn]
Duan, Hui-Ling [VerfasserIn]
Zhang, Jing [VerfasserIn]
Dang, Fu-Quan [VerfasserIn]
Zhang, Liqin [VerfasserIn]
Zhang, Zhi-Qi [VerfasserIn]

Links:

Volltext

Themen:

Fluorescent Dyes
Journal Article
Peptides
RNA, Viral
Research Support, Non-U.S. Gov't
Stilbenes
Tetraphenylethylene

Anmerkungen:

Date Completed 16.02.2021

Date Revised 16.02.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acs.analchem.0c03010

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM31472835X