Aminoglycoside-nucleic acid interactions: The case for neomycin

Aminoglycoside antibiotics are bactericidal drugs that have been at the forefront of antimicrobial therapy for almost five decades. The past decade (1990-2000) saw a resurgence in aminoglycoside-based drug development as their chemistry/mechanism of action became better understood. This work, however, had almost exclusively focused on targeting RNA. This review summarizes new developments (past 4-5 years) in aminoglycoside-nucleic acid interactions in the broader context of nucleic acid selectivity, not just RNA. Aminoglycoside binding to A-form nucleic acid structures is discussed, as is the development of novel conjugates for major-minor groove recognition of B-form DNA. Neomycin is chosen as the representative aminoglycoside and is revealed here to be an underutilized scaffold in nucleic acid recognition.