Open AccessIdentification of the adduct between a 4-aza-3-ene-1,6-diyne and DNA using electrospray ionization mass spectrometry
Author(s) -
Courtney L. Sherman,
Sarah E. Pierce,
Jennifer S. Brodbelt,
Bodin Tuesuwan,
Sean M. Kerwin
Publication year - 2006
Publication title -
journal of the american society for mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.961
H-Index - 127
eISSN - 1879-1123
pISSN - 1044-0305
DOI - 10.1016/j.jasms.2006.05.015
Subject(s) - enediyne , chemistry , electrospray ionization , adduct , nucleobase , oligonucleotide , mass spectrometry , stereochemistry , dna , cytosine , tandem mass spectrometry , cleavage (geology) , combinatorial chemistry , organic chemistry , chromatography , biochemistry , geotechnical engineering , fracture (geology) , engineering
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.