Opposite Charges, Different Stability: Telomeric G-Quadruplexes in Nanoconfinement

In this study, the effect of the chemical nature of confinement on the folding and thermal stability of the telomere G-quadruplex (G4) has been investigated by studying the folding pattern of different telomeric derived DNA sequences with varying numbers and arrangements of thymine loop nucleobases in the presence of anionic and cationic nanosized water pools. The findings suggest that both anionic and cationic water pools fold the telomere sequences into a G4 of the same topology. However, the thermal stability of the folded G4 in the cationic water pool is significantly lower than that in the anionic case. The overall data indicate that the topology of the folded G4 is insensitive to the nature of the confinement; however, the thermal stability of the folded telomeric G4 depends significantly on the chemical nature of the confinement. It is plausible that the interfacial water inside the cationic water pools has a different orientation and hydrogen bonding than in the case of anionic water pools, which may cause the different thermal stabilities of the G4 on these two water pools. These findings may be important in understanding the folding and stability of telomere G4 inside a confined cellular system.