ESIイオントラップによるDNAとドラッグの相互作用解析
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概要
- 論文の詳細を見る
We developed an assay method that utilizes ESI and ion trap mass spectrometry to rapidly determine the binding nature of drugs with oligodeoxynucleotides and to assess their relative affinities, stoichiometries and specificities in non-covalent interactions. Selectivity experiments show that the drugs H2TMpyP and CuTMpyP bind via mixed modes, whereasFeTMpyP and MnTMpyP interact by groove binding only. Competitive binding experiments show that the order for the drugs with duplex 5′ATATAT3′ was H2TMpyP-CuTMpyP>FeTMpyP-MnTMpyP. We also investigated the gas-phase stability of duplex oligodeoxynucleotides and the non-covalent complexes by monitoring the dissociation profiles of those non-covalent associations as a function of collision energy in the ion-trap mass spectrometer. We defined a half-wave collision energy which corresponds to the collision energy (in percentage of the maximum tickling voltage) at which the relative abundance of the complex ion had dropped to 50% and used this as an estimate of the gas-phase stability. The gas-phase stability of double-stranded oligonucleotide correlates with the number of H-bonds within the duplex. The noncovalent complexes of the drugs (Distamycin A, Actinomycin D, and Mn(III)TMpyP) and the duplex oligonucleotides are more stable in the gas phase than the duplexes themselves.
- 日本質量分析学会の論文
- 2000-06-01
著者
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グロス マイケル
Department Of Chemistry Washington University
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渋江 俊道
Materials Characterization Central Laboratory Waseda University
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ウォン カイティ
Department of Chemistry, Washington University
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ウォン カイティ
Department Of Chemistry Washington University