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Specific recognition of DNA bulge structure by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry
Author(s) -
Chen YuJu,
Chen PoJui,
Wang HsuehTing,
Cheng ChienChung
Publication year - 2004
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1377
Subject(s) - chemistry , deoxyribose , mass spectrometry , cleavage (geology) , matrix assisted laser desorption/ionization , moiety , dna , combinatorial chemistry , stereochemistry , desorption , chromatography , organic chemistry , biochemistry , geotechnical engineering , adsorption , fracture (geology) , engineering
This study reports a novel approach utilizing an octahedral Co II (HAPP)(TFA) 2 reagent in the presence of H 2 O 2 with analysis by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) to serve as an efficient probe for bulged DNA structures. Elucidation of DNA bulge‐specific recognition pathways and cleavage mechanisms is demonstrated by characterization of bulge‐specific cleavage products and other backbone lesion fragments. The cleavage specificity of Co II (HAPP)(TFA) 2 /H 2 O 2 arises from sugar oxidative strand scission, for which the position of the abstracted hydrogen is unambiguously determined as the 4′‐H of the deoxyribose moiety. Furthermore, differentiation between bulge‐specific recognition and diffusion‐controlled non‐selective cleavage can be clarified through time‐dependent MALDI‐TOFMS studies. The present results demonstrate that MALDI‐TOFMS can be a sensitive and efficient technique for complex mechanistic studies of this kind, providing information for future rational drug design targeting bulged DNA structures. Copyright © 2004 John Wiley & Sons, Ltd.