Journal Article

Development of Fluorescent Turn-On Probes for CAG-RNA Repeats

Au-Yeung, Ho Yu, Lau, Matthew Ho Yan, Chan, Ho Yin Edwin, Wong, Chun-Ho

2022

Overview

Fluorescent sensing of nucleic acids is a highly sensitive and efficient bioanalytical method for their study in cellular processes, detection and diagnosis in related diseases. However, the design of small molecule fluorescent probes for the selective binding and detection of RNA of a specific sequence is very challenging because of their diverse, dynamic, and flexible structures. By modifying a bis(amidinium)-based small molecular binder that is known to selectively target RNA with CAG repeats using an environment-sensitive fluorophore, a turn-on fluorescent probe featuring aggregation-induced emission (AIE) is successfully developed in this proof-of-concept study. The probe (DB-TPE) exhibits a strong, 19-fold fluorescence enhancement upon binding to a short CAG RNA, and the binding and fluorescence response was found to be specific to the overall RNA secondary structure with A·A mismatches. These promising analytical performances suggest that the probe could be applied in pathological studies, disease progression monitoring, as well as diagnosis of related neurodegenerative diseases due to expanded CAG RNA repeats.

• Publisher: MDPI AG,MDPI
• Subject: AIE / Analysis / Bioanalysis / CAG repeats / Chromatography / Communication / Degeneration / Diagnosis / Disease / DNA probes / Emission analysis / Ethanol / Flexible structures / Fluorescence / Fluorescent Dyes - chemistry / Fluorescent indicators / fluorescent probe / Gene mutations / Health aspects / Methods / Nervous system / Neurodegenerative diseases / Neurotoxicity / Nucleic Acids / Nucleotide sequence / Polyglutamine / Probes / Protein structure / Proteins / Ribonucleic acid / RNA / RNA probes / Secondary structure / Selective binding / Solvents / Spectrometry, Fluorescence / Toxicity / Trinucleotide repeats