著者

渋江 俊道 ウォン カイティ グロス マイケル

出版者

The Mass Spectrometry Society of Japan

雑誌

質量分析 = Mass spectroscopy (ISSN:13408097)

巻号頁・発行日

vol.48, no.3, pp.221-227, 2000-06-01

参考文献数

20

被引用文献数

3

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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 <I>via</I> 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.