Molecular Recognition of tRNA with 1-Naphthyl Acetyl Spermine, Spermine and Spermidine: A Thermodynamic, Biophysical and Molecular Docking Investigative Approach.

A major thrust of anticancer therapeutics is the dynamic quest for small molecules that binds and modifies nucleic acids and proteins effectively. The role of tRNA in the protein translational machinery and the influence of polyamines on the interaction of acylated and deacylated tRNA to ribosomes,47-48 make polyamine-tRNA interactions conspicuous. Therefore, we have studied the interaction of two biogenic polyamines spermine and spermidine with tRNAPhe and compared the interaction with the polyamine analog, 1-naphthyl acetyl spermine to fathom the thermodynamic and structural basis of the binding interaction. The binding affinity of spermine was comparable to 1-naphthyl acetyl spermine and both were greater than spermidine. The interactions led to significant thermal stabilization of the tRNAPhe and an increase in the enthalpy of transition. All the interactions were exothermic in nature and displayed prominent enthalpy-entropy compensation behavior. The entropy driven nature of the interaction, the structural perturbations observed in circular dichroism spectra and docking results proved that the polyamines were bound in the groove of the anticodon arm of tRNA(Phe). The amine groups in the polyamines were involved in extensive electrostatic, H-bonding and van der Waals interactions with the tRNAPhe molecule. The naphthyl group of 1-naphthyl acetyl spermine made additional stacking interaction with G24 and G26 of tRNAPhe, which was absent in the case of spermine and spermidine. Thus, the results demonstrate that the polyamine analog has a strong capability to target the same binding sites as biogenic polyamines but without substituting for the functions played by them, which may lead to exhibition of selective anti-cancer cytotoxicity. Therefore, this study on the interaction of 1-napthyl acetyl spermine with tRNAPhe potentiates further development of this analog as an anti-cancer therapeutic.