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 (K(a) approximately 10(8)M(-1)) as determined by isothermal titration calorimetry.
Arya
Dev P
DP
Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634, USA.
Coffee
R Lane
RL
Xue
Liang
L
D002151:Calorimetry; D004247:DNA / Q000737:chemistry*; D019281:Dimerization; D009355:Neomycin / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship; D014031:Tobramycin / Q000737:chemistry*
C051802:triplex DNA; D004247:DNA; D009355:Neomycin; D014031:Tobramycin