Abstract
Molecules capable of inducing self-structure in poly(A) may arrest protein synthesis by preventing poly(A) chain elongation thereby inhibiting the function of mRNA. We examined whether new methylene blue can induce such structural organization in single stranded poly(A) and compared the results with those of the phenothiazinium dyes thionine and toluidine blue O. Strong association between the dyes and poly(A) was revealed from the spectroscopy and cyclic voltammetry. Thionine has a higher affinity compared to toluidine blue O and new methylene blue at 50 mM and 100 mM, but at 200 mM [Na+] new methylene blue exhibited the highest binding affinity. Negative enthalpy and positive entropy changes, and enthalpy-entropy compensation behaviour were characteristic features for the complexation. Involvement of hydrophobic forces in the binding process is correlated to the negative heat capacity changes. Differential scanning calorimetry and circular dichroism results revealed that the dyes bind poly(A) and induce a stable secondary structure with a melting temperature of 333.15 K. The binding constants increased in the range of 50–200 mM [Na+]. Molecular docking results revealed that not only van der Waals forces of attraction but hydrogen bonding also plays a crucial role in dye-poly(A) binding. Recognition and binding of small molecules to single stranded poly(A) may present a new avenue for therapeutic intervention.
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