Evaluation of relative DNA binding affinities of anthrapyrazoles by electrospray ionization mass spectrometry

被引:17
作者
Smith, Suncerae I.
Guziec, Lynn J.
Guziec, Frank S., Jr.
Hasinoff, Brian B.
Brodbelt, Jennifer S. [1 ]
机构
[1] Univ Texas, Dept Chem & Biochem, Austin, TX 78712 USA
[2] SW Univ, Dept Chem, Georgetown, TX 79626 USA
[3] Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada
来源
JOURNAL OF MASS SPECTROMETRY | 2007年 / 42卷 / 05期
关键词
anthrapyrazole; DNA; anticancer drug; intercalator; ESI-MS;
D O I
10.1002/jms.1205
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Binding interactions of a new series of anthrapyrazoles (APs) with DNA were evaluated by electrospray ionization mass spectrometry (ESI-MS). Relative binding affinities were estimated from the ESI-MS data based on the fraction of bound DNA for DNA/anthrapyrazole mixtures, and they show a correlation to the shift in melting point of the DNA measured from a previous study. Minimal sequence specificity was observed for the series of anthrapyrazoles. Upon collisionally activated dissociation of the duplex/anthrapyrazole complexes, typically ejection of the ligand was the dominant pathway for most of the complexes. However, for complexes containing AP2 or mitoxantrone, strand separation with the ligand remaining on one of the single strands was observed, indicative of a different binding mode or stronger binding. Copyright (c) 2007 John Wiley & Sons, Ltd.
引用
收藏
页码:681 / 688
页数:8
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