Locating the binding sites of two aminobenzoic acid derivatives on tRNA: drug binding efficacy and RNA structure

Abstract

The binding of tRNA to aminobenzoic acid derivatives DAB-0 (N'-[4-(2,5-dioxo-pyrrolidin-1-yl)-benzoyl]-hydrazine carboxylic acid tert-butyl ester) and DAB-1 (N'-[4-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-benzoyl]-hydrazine carboxylic acid tert-butyl ester) was investigated in aqueous solution at physiological pH. Thermodynamic parameters ΔH⁰ −4.8 to −4.30 (kJ mol⁻¹), ΔS⁰ 24.20 to 22 (J mol⁻¹K^–1) and ΔG⁰ −12 to −11.40 (kJ mol⁻¹) showed that DAB-0 and DAB-1 readily bind tRNA via ionic interactions with DAB-1 forming stronger tRNA adducts. Similar binding sites to A-T and G-C bases were located with DAB-0 and DAB-1. The binding efficacy ranged from 40% to 50%. No alteration of tRNA conformation was detected upon drug complexation.

Communicated by Ramaswamy H. Sarma

Keywords:

• Aminobenzoic acid
• tRNA
• binding efficacy
• thermodynamic analysis
• modeling

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We thank the Natural Sciences and Engineering Research Council of Canada (NSERC) for the financial support. This study was also supported by grants from the Cancer Institute of Canadian Institutes of Health Research (CIHR; number 392334) the Cancer Research Society (CRS; number 22471) and Aligo Innovation (number 150923) to C. Reyes-Moreno and G. Bérubé.