| Autor: |
Choudhary NK; Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India., Gupta S; School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India., Das G; Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India., Sahoo A; Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India., Harikrishna S; Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, United States., Sinha S; School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India., Gore KR; Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India. |
| Abstrakt: |
Red fluorescent protein (RFP)-based fluorescent probes that can selectively interact with specific nucleic acids are of great importance for therapeutic and bioimaging applications. Herein, we have reported the synthesis of RFP chromophores for selective recognition of G-quadruplex nucleic acids in vitro and ex vivo. We identified DFHBI-DM as a fluorescent turn-on probe that binds to the dimeric NG16 parallel quadruplex with superior selectivity and sensitivity over various parallel, antiparallel, and hybrid topologies. The binding of DFHBI-DM to NG16 exhibited excellent photophysical properties, including high binding affinity, large Stokes shift, high photostability, and quantum yield. The MD simulation study supports the 1:1 binding stoichiometry. It confirms the planar conformation of DFHBI-DM , which makes strong binding interactions with a flat quartet of NG16 compared to other antiparallel and hybrid topologies. The cell imaging and MTT assays revealed that DFHBI-DM is a biocompatible and efficient fluorescent probe for intracellular imaging of NG16. Overall, these results demonstrated that DFHBI-DM could be an effective fluorescent G4-stabilizing agent for the dimeric NG16 parallel quadruplex, and it could be a promising candidate for further exploration of bioimaging and therapeutic applications. |
