From triplex to B-form duplex stabilization: reversal of target selectivity by aminoglycoside dimers |
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Authors: | Arya Dev P Coffee R Lane Xue Liang |
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Institution: | Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634, USA. |
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Abstract: | 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. |
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