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Tandem mass spectrometry of platinated quadruplex DNA
Author(s) -
Stucki Silvan R.,
Nyakas Adrien,
Schürch Stefan
Publication year - 2011
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.2019
Subject(s) - chemistry , g quadruplex , tandem mass spectrometry , dna , mass spectrometry , dissociation (chemistry) , fragmentation (computing) , telomere , stereochemistry , electrospray ionization , rna , combinatorial chemistry , biophysics , biochemistry , chromatography , gene , organic chemistry , biology , computer science , operating system
Quadruplexes are higher‐order structures formed by G‐rich DNA strands that are involved in various processes of cell cycle regulation, such as control of telomere length and participation in gene regulation. Because of these central biological functions, quadruplex DNA represents a promising target for cancer therapy, e.g. by applying organometallic drugs, such as cisplatin. High‐resolution electrospray tandem mass spectrometry is evaluated as a technique for exploring structural features of unplatinated and platinated quadruplexes. Results of experiments on tetramolecular, bimolecular and monomolecular quadruplexes provide information about the extent of platination and the binding sites of the drug. The dissociation behavior of the different types of quadruplexes is compared. Tetramolecular quadruplexes were found to weave out a strand end in order to provide a platination site, and their fragmentation is characterized by the release of an unplatinated strand and the formation of a platinated triplex. Partial opening of the structure in combination with the loss of small fragments leads to truncated quadruplex ions. For the bimolecular quadruplexes studied, strand separation is the predominant dissociation pathway. Depending on the loop sequence, cross‐linking of the loops by cisplatin is demonstrated. Distinct differences in the product ion spectra of unannealed and annealed monomolecular sequences provide proof of quadruplex formation and show that platination preferentially occurs at the terminal regions. Copyright © 2011 John Wiley & Sons, Ltd.