A great part of our research is focused on the application of tandem mass spectrometry for the structural investigation of oligonucleotides and their analogues. Modified oligonucleotides bear a great potential for therapeutic applications and diagnostic purposes. Since classical sequencing methods based on enzymatic or chemical degradation often fail in the case of modified oligonucleotides, alternative techniques are needed. A goal of our research is to fill this gap and to develop novel protocols based on tandem mass spectrometry for the characterization of nucleic acids. This also requires elucidation of the fundamental mechanistic processes involved in the gas-phase dissociation of selected compounds. In 2005, we demonstrated how collisionally activated RNA ions dissociate into the sequence-defining c- and y-type fragments. Other analytical work was focused on a number of DNA analogues, e.g. methylphosphonate-oligonucleotides and sugar-modified nucleic acids, which are of therapeutic interest.
Y. Hari, C.J. Leumann, S. Schürch. What hinders electron transfer dissociation (ETD) of DNA cations? J. Am. Soc. Mass Spectrom. 2017, 28, 2677-2685. 10.1007/s13361-017-1791-z.
S. Schürch. Characterization of Nucleic Acids by Tandem Mass Spectrometry - The Second Decade (2004 - 2013): From DNA to RNA and Modified Sequences. Mass Spectrom. Rev. 2016, 35, 483-523. 10.1002/mas.21442.
A. Nyakas, R. P. Eberle, S. R. Stucki, S. Schürch. More than charged base loss - revisiting the fragmentation of highly charged oligonucleotides. J. Am. Soc. Mass Spectrom. 2014, 25, 1155-1166. 10.1007/s13361-014-0873-4
Y. Hari, A. Nyakas, S. R. Stucki, S. Schürch. Elucidation of nucleic acid - drug interactions by tandem mass spectrometry. Chimia. 2014, 68, 164-167. 10.2533/chimia.2014.164
S. R. Stucki, C. Désiron, A. Nyakas, S. Marti, C. J. Leumann, S. Schürch. Gas-phase Dissociation of homo-DNA Oligonucleotides. J. Am. Soc. Mass Spectrom. 2013, 24, 1997-2006. 10.1007/s13361-013-0729-3
A. Nyakas, L. C. Blum, S. R. Stucki, J.-L. Reymond, S. Schürch. OMA and OPA - software-supported mass spectra analysis of native and modified nucleic acids. J. Am. Soc. Mass Spectrom. 2013, 24, 249-256. 10.1007/s13361-012-0529-1.
S. Monn, S. Schürch. New Aspects of the Fragmentation Mechanisms of Unmodified and Methylphosphonate-Modified Oligonucleotides. J. Am. Soc. Mass Spectrom. 2007, 18, 984-990. 10.1016/j.jasms.2007.02.006
S. Schürch, J. M. Tromp, S. Monn. Mass Spectrometry of Oligonucleotides. Nucleosides, nucleotides Nucleic Acids, 2007, 26, 1629-1633. 10.1080/15257770701549053
J. M. Tromp, S. Schürch. Electrospray ionization tandem mass spectrometry of biphenyl-modified oligo(deoxy)ribonucleotides. Rapid Commun. Mass Spectrom. 2006, 20, 2348-2354. 10.1002/rcm.2596
J. M. Tromp, S. Schürch. Gas-phase dissociation of oligoribonucleotides and their analogs studied by electrospray ionization tandem mass spectrometry. J. Am. Soc. Mass Spectrom. 2005, 16, 1262-1268.
S. Schürch, E. Bernal-Méndez, C. J. Leumann. Electrospray tandem mass spectrometry of mixed-sequence RNA/DNA oligonucleotides. J. Am. Soc. Mass Spectrom. 2002, 13, 936-945.