Identification of the Adduct Between a 4-Aza-3-ene-1,6-diyne and DNA Using Electrospray Ionization Mass Spectrometry

详细信息    查看全文

• 作者：Courtney L. Sherman ; Sarah E. Pierce ; Jennifer S. Brodbelt ; Bodin Tuesuwan and Sean M. Kerwin
• 刊名：Journal of the American Society for Mass Spectrometry
• 出版年：2006
• 出版时间：October 2006
• 年：2006
• 卷：17
• 期：10
• 页码：1342-1352
• 全文大小：725 K

文摘

The interactions between a novel enediyne [1-methyl-2-(phenylethynyl)-3-(3-phenylprop-2-ynyl)-3H-benzimidazolium] (1) and various cytosine-containing oligonucleotides were studied using electrospray ionization mass spectrometry (ESI-MS) in a flow injection analysis mode useful for small volumes. This enediyne ligand, developed as a potential alternative to the highly cytotoxic natural enediynes, some of which have been successfully used as anti-tumor agents, has previously been shown to interact with DNA through frank strand scission as well as via the formation of adducts that lead to 2′-deoxycytidine-specific cleavage. Through ESI-MS, the structures of these adducts were examined and a sequence dependence of the 2′-deoxycytidine-specific cleavage was noted. Collisionally activated dissociation of the observed adducts confirmed the strength of the interactions between the enediyne and DNA and supports a direct linkage between the enediyne and the cytosine nucleobase, likely the result of a nucleophilic attack of the phenylethynyl group by the cytosine amine.