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; binding efficacy; modeling; tRNA; thermodynamic analysis.