ac3c01194_si_001.pdf (12.37 MB)
An Effective Docking-Guided Strategy for Rational Tailoring of Fluorescent Aptamer Switches of Dimethylindole Red Analogue
journal contributionposted on 2023-04-28, 12:09 authored by Yangzi Zhang, Longjiao Zhu, Xuan Ma, Siyue Zhu, Yongqiang Ma, Sabir Hussain, Xiaoyun He, Wentao Xu
The light-up aptamer-dimethylindole red (DIR) complexes have been applied in biochemistry analysis as promising signal transduction tools. However, the unfavorable repulsions between DIR and the long-sequence aptamer switch hinder the complex’s further development, and it is urgent to engineer a feasible and efficient strategy for synchronously and rationally adjusting the DIR chemical structure and the DIR aptamer performance. Herein, we communicate a versatile docking-guided rational tailoring strategy to effectively upgrade a DNA aptamer which specifically turns on the fluorescence of a synthesized amino-functionalized DIR analogue (NH2-DIR). After optimizing with three-level tailoring strategies including molecule docking-guided tailoring, coarse tailoring, and fine tailoring, the NH2-DIR aptamer switch with higher binding affinity and specificity, considerable fluorescence-activation ability, and 40% shortened length was obtained. Integrating the experimental and docking results, the binding mechanism between NH2-DIR and the tailored aptamer was deciphered via three types of interactions.
higher binding affinityfunctionalized dir analoguedir chemical structurefluorescent aptamer switchesdimethylindole red analoguedir aptamer performancedimethylindole redbinding mechanismtailored aptamerdna aptamerversatile dockingunfavorable repulsionssynthesized aminospecifically turnsshortened lengthrationally adjustingrational tailoringguided tailoringguided strategyfine tailoringefficient strategyeffectively upgradeeffective dockingdocking resultscomplex ’coarse tailoringbiochemistry analysisactivation ability