Interaction of tRNA with antitumor polyamine analogues

Abstract

We studied the interaction between tRNA and three polyamine analogues (1,11-diamino-4,8-diazaundecane·4HCl (333), 3,7,11,15-tetrazaheptadecane·4HCl (BE-333), and 3,7,11,15,19-pentazahenicosane·5HCl (BE-3333)) using FTIR, UV-visible, and CD spectroscopic methods. Spectroscopic evidence showed that polyamine analogues bound tRNA via guanine N7, adenine, uracil O2, and the backbone phosphate (PO2–) groups, while the most reactive sites for biogenic polyamines were guanine N7/O6, adenine N7, uracil O2, and sugar 2′-OH groups as well as the backbone phosphate group. The binding constants of polyamine analogue – tRNA recognition were lower than those of the biogenic polyamine – tRNA complexes, with K333= 2.8 (±0.5) × 104, KBE-333= 3.7 (±0.7) × 104, KBE-3333= 4.0 (±0.9) × 104, Kspm= 8.7 (±0.9) × 105, Kspd= 6.1 (±0.7) × 105, and Kput= 1.0 (±0.3) × 105mol/L. tRNA remained in the A-family conformation; however, it aggregated at high polyamine analogue concentrations.