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

P. Bourassa, T. J. Thomas, J. Bariyanga, H. A. Tajmir-Riahi

Research output: Contribution to journalArticle

6 Scopus citations

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 languageEnglish (US)
Pages (from-to)692-698
Number of pages7
JournalInternational Journal of Biological Macromolecules
Volume72
DOIs
StatePublished - Jan 1 2015

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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

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