Breast anticancer drug tamoxifen and its metabolites bind tRNA at multiple sites

The binding sites of breast anticancer drug tamoxifen and its metabolites with tRNA were located by FTIR, CD, UV-visible, and fluorescence spectroscopic methods and molecular modeling. Structural analysis showed that tamoxifen and its metabolites bind tRNA at several binding sites with overall binding constants of Ktam-tRNA = 5.2 (±0.6) × 104 M−1, K4-hydroxytam-tRNA = 6.5 (±0.5) × 104 M−1 and Kendox-tRNA = 1.3 (±0.2) × 104 M−1. The number of binding sites occupied by drug molecules on tRNA were 1 (tamoxifen), 0.8 (4-hydroxitamoxifen) and 1.2 (endoxifen). Docking showed the participation of several nucleobases in drug-tRNA complexes with the free binding energy of −4.31 (tamoxifen), −4.45 (4-hydroxtamoxifen) and −4.38 kcal/mol (endoxifen). The order of binding is 4-hydroxy-tamoxifen > tamoxifen > endoxifen. Drug binding did not alter tRNA conformation from A-family structure, while biopolymer aggregation occurred at high drug concentration.