From triplex to B-form duplex stabilization: reversal of target selectivity by aminoglycoside dimers

Aminoglycosides have been shown to target A-form nucleic acids. Our work has previously shown that neomycin (and other aminoglycosides) bind and stabilize DNA/RNA triplexes and other A-form nucleic acids. We report herein the unexpected B-form duplex stabilization shown by aminoglycoside dimers (neomycin–neomycin and neomycin–tobramycin). The dimers are highly selective for AT rich duplexes and show high affinity (Ka 108 M−1) as determined by isothermal titration calorimetry.