Identification of the adduct between a 4-Aza-3-ene-1,6-diyne and DNA using electrospray ionization mass spectrometry.
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.
Sherman
Courtney L
CL
Department of Chemistry and Biochemistry, University of Texas, 1 University Station A5300, 78712, Austin, TX, USA.
Pierce
Sarah E
SE
Department of Chemistry and Biochemistry, University of Texas, 1 University Station A5300, 78712, Austin, TX, USA.
Brodbelt
Jennifer S
JS
Department of Chemistry and Biochemistry, University of Texas, 1 University Station A5300, 78712, Austin, TX, USA. jbrodbelt@mail.utexas.edu.
Tuesuwan
Bodin
B
Division of Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas, USA.
Kerwin
Sean M
SM
Division of Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas, USA.
D000480:Alkynes / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry*; D018736:DNA Adducts / Q000032:analysis*; D004591:Electrophoresis, Polyacrylamide Gel; D007202:Indicators and Reagents; D009841:Oligonucleotides / Q000032:analysis; D010880:Piperidines / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
C522230:1-methyl-2-(phenylethynyl)-3-(3-phenylprop-2-ynyl)-3H-benzimidazolium; D000480:Alkynes; D001562:Benzimidazoles; D018736:DNA Adducts; D007202:Indicators and Reagents; D009841:Oligonucleotides; D010880:Piperidines