title: Specific recognition of DNA bulge structure by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
abstract: This study reports a novel approach utilizing an octahedral CoII(HAPP)(TFA)2 reagent in the presence of H2O2 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 CoII(HAPP)(TFA)2/H2O2 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.
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei, Taiwan 11529, ROC. yjchen@chem.sinica.edu.tw
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Po-Jui
authors.initials: PJ
authors.lastname: Chen
authors.forename: Hsueh-Ting
authors.initials: HT
authors.lastname: Wang
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Cheng
mesh_terms: D001483:Base Sequence; D003035:Cobalt / Q000737:chemistry; D004278:DNA, Superhelical / Q000032:analysis / Q000737:chemistry*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D004278:DNA, Superhelical; D003035:Cobalt