Recognition of a cognate RNA aptamer by neomycin B: quantitative evaluation of hydrogen bonding and electrostatic interactions

Aminoglycosides are an important class of antibiotic that selectively targe t RNA structural motifs, Recently we have demonstrated copper derivatives o f aminoglycosides to be efficient cleavage agents for cognate RNA motifs, T o fully develop their potential as pharmaceutical agents it is necessary to understand both the structural mechanisms used by aminoglycosides to targe t RNA, and the relative contributions of hydrogen bonding and electrostatic interactions to recognition selectivity. Herein we report results from a c alorimetric analysis of a stem-loop 23mer RNA aptamer complexed to the amin oglycoside neomycin B. Key thermodynamic parameters for complex formation h ave been determined by isothermal titration calorimetry, and from the metal -ion dependence of these binding parameters the relative contributions of e lectrostatics and hydrogen bonding toward binding affinity have been assess ed. The principal mechanism for recognition and binding of neomycin B to th e RNA major groove is mediated by hydrogen bonding.