Differentiation and Distributions of DNA/Cisplatin Crosslinks by Liquid Chromatography-Electrospray Ionization-Infrared Multiphoton Dissociation Mass Spectrometry

作者：Xu Zhe; Brodbelt Jennifer S^*

来源：Journal of the American Society for Mass Spectrometry, 2014, 25(1): 71-79.

DOI：10.1007/s13361-013-0755-1

• Tandem mass spectrometry
• Cisplatin
• Oligodeoxynucleotides
• Photodissociation
• Hairpin

Liquid chromatography-electrospray ionization-infrared multiphoton dissociation (IRMPD) mass spectrometry was developed to investigate the distributions of intrastrand crosslinks formed between cisplatin and two oligodeoxynucleotides (ODNs), d(A(1)T(2)G(3)G(4)G(5)T(6)A(7)C(8)C(9)C(10)A(11)T(12)) (G3-D) and its analog d(A(1)T(2)G(3)G(4)G(5)T(6)T(7)C(8)C(9)C(10)A(11)T(12)) (G3-H), which have been reported to adopt different secondary structures in solution. Based on the formation of site-specific fragment ions upon IRMPD, two isobaric crosslink products were differentiated for each ODN. The preferential formation of G(3)G(4) and G(4)G(5) crosslinks was determined as a function of reaction conditions, including incubation temperature and presence of metal ions. G3-D consistently exhibited a greater preference for formation of the G(4)G(5) crosslink compared with the G3-H ODN. The ratio of G(3)G(4):G(4)G(5) crosslinks increased for both G3-D and G3-H at higher incubation temperatures or when metal salts were added. Comparison of the IRMPD fragmentation patterns of the unmodified ODNs and the intramolecular platinated crosslinks indicated that backbone cleavage was significantly suppressed near the crosslink.

• 出版日期2014-1