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

The role of tRNA in protein translational machinery and the influence of polyamines on the interaction of acylated and deacylated tRNA with ribosomes make polyamine-tRNA interaction conspicuous. We studied the interaction of two biogenic polyamines, spermine (SPM) and spermidine (SPD), with tRNA^Phe and compared the results to those of the analogue 1-naphthyl acetyl spermine (NASPM). The binding affinity of SPM was comparable to that of NASPM; both were higher than that of SPD. The interactions led to significant thermal stabilization of tRNA^Phe 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, and docking results proved that the polyamines were bound in the groove of the anticodon arm of tRNA^Phe. The amine groups of polyamines were involved in extensive electrostatic, H-bonding, and van der Waals interactions with tRNA^Phe. The naphthyl group of NASPM showed an additional stacking interaction with G24 and G26 of tRNA^Phe, which was absent in others. The results demonstrate that 1-naphthyl acetyl spermine can target the same binding sites as the biogenic polyamines without substituting for the functions played by them, which may lead to exhibition of selective anticancer cytotoxicity.