Location of multiple binding sites for testo and testo–Pt(II) with tRNA

Abstract

We report the binding of testo and testo–Pt(II) complexes (testosterone derivatives) with tRNA in aqueous solution at physiological pH. Thermodynamic parameter ΔH₀ −8 to −3 (kJ mol⁻¹), ΔS₀ 35 to 18 (J mol⁻¹K⁻¹) and ΔG₀ −14 to −13 (kJ mol⁻¹) and other spectroscopic results showed drug–tRNA binding occurs via ionic contacts with testo–Pt(II) forming more stable tRNA complexes in comparison to testo: K_testo–Pt(II)–tRNA= 3.2 (± 0.9) × 10⁵ M⁻¹ > K_testo-tRNA= 2.1 (± 0.7) × 10⁵ M⁻¹. Molecular modeling showed multiple binding sites for testo and testo–Pt(II) on tRNA molecule. Some of the useful molecular descriptors are calculated. Major structural changes were observed for biopolymers upon drug complexation, while tRNA remains in the A-family structures.

Keywords:

• tRNA
• testo–Pt(II)
• conjugation
• spectroscopy
• docking

Acknowledgments

The authors thank the Natural Sciences and Engineering Research Council of Canada (NSERC) for the financial support.

Disclosure statement

No potential conflict of interest was reported by the authors.