Evidence for the binding mode of porphyrins to G-quadruplex DNAw

Interactions of porphyrin derivatives 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)-21H,23Hporphyrin (TMPyP4) and 5,10,15,20-tetrakis(N-propylpyridinium-4-yl)-21H,23H-porphyrin (TPrPyP4) with human telomeric AG3(T2AG3)3 G-quadruplex DNAs in 150 mM K -containing buffer in the presence or absence of 40% molecular crowding agent poly(ethylene glycol) (PEG 200) were studied by absorption titration fitting and time-resolved fluorescence spectroscopy. The results show that two TMPyP4 (or TPrPyP4) molecules bind to antiparallel/parallel hybrid structure of AG3(T2AG3)3 G-quadruplex by end-stacking and outside groove binding modes in the absence of PEG. Interestingly, in the presence of PEG one porphyrin molecule is stacked between two parallel AG3(T2AG3)3 Gquadruplexes to form a sandwich structure, another porphyrin molecule is bound to the groove of the G-quadruplex. The interactions of TMPyP4 with different structures of AG3(T2AG3)3 G-quadruplex are non cooperative, the binding constants of two independent binding sites are 1.07 10 and 4.42 10 M 1 for an antiparallel/parallel hybrid structure of AG3(T2AG3)3, 8.67 10 and 2.26 10 M 1 for parallel-stranded AG3(T2AG3)3 G-quadruplex. Conversely, the two binding sites are cooperative for TPrPyP4, the apparent association constants are 5.58 10 and 1.24 10 M 1 for parallel-stranded and antiparallel/ parallel hybrid structures of AG3(T2AG3)3 G-quadruplex, respectively.