Kar, AshishAshishKarPraneeth, N. V.S.N. V.S.PraneethKhatua, SaumyakantiSaumyakantiKhatuaDatta, BhaskarBhaskarDatta2025-08-312025-08-312023-07-1310.1021/acs.jpclett.3c010032-s2.0-85164625634https://d8.irins.org/handle/IITG2025/2672437409750Single-molecule measurements are crucial for studying the interactions between G-quadruplex (GQ) DNA and ligands, as they provide higher resolution and sensitivity compared to those of bulk measurements. In this study, we employed plasmon-enhanced fluorescence to investigate the real-time interaction between the cationic porphyrin ligand TmPyP4 and different topologies of telomeric GQ DNA at the single-molecule level. By analyzing the time traces of the fluorescence bursts, we extracted dwell times for the ligand. For parallel telomeric GQ DNA, the dwell time distribution followed a biexponential fit, yielding mean dwell times of 5.6 and 18.6 ms. For the antiparallel topology of human telomeric GQ DNA, plasmon-enhanced fluorescence of TmPyP4 was observed, with dwell time distributions following a single-exponential fit and a mean dwell time of 5.9 ms. Our approach allows the nuances of GQ-ligand interactions to be captured and holds promise for studying weakly emitting GQ ligands at the single-molecule level.falseArticle194871856321-632713 July 20235arJournal5WOS:001023572500001