Abstract
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)×104M-1, K4-hydroxytam-tRNA=6.5 (±0.5)×104M-1 and Kendox-tRNA=1.3 (±0.2)×104M-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 -4.38kcal/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.
Original language | English (US) |
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Pages (from-to) | 692-698 |
Number of pages | 7 |
Journal | International Journal of Biological Macromolecules |
Volume | 72 |
DOIs | |
State | Published - Jan 1 2015 |
All Science Journal Classification (ASJC) codes
- Structural Biology
- Biochemistry
- Molecular Biology
- Economics and Econometrics
- Energy(all)
Keywords
- 4-hydroxtamox4-hydroxytamoxifen
- Binding site
- CDcircular dichroism
- Endoxendoxifen
- FTIRFourier transform infrared spectroscopy
- Modeling
- Spectroscopy
- TRNA
- Tamoxifen
- Tamoxtamoxifen