Activation of oligonucleotide polyanions using collisions, electrons and photons in a timsOmni platform

Rapport Preprint Activation of oligonucleotide polyanions using collisions, electrons and photons in a timsOmni platform eng 2025-11-10 author Rosu Frédéric Johanna R 0000-0003-3674-7539 417908 Section des sciences pharmaceutiques (FARMA) author Chiba Rim 419160 Section des sciences pharmaceutiques (FARMA) author Mani Mallika Arjun 429515 Section des sciences pharmaceutiques (FARMA) author Smyrnakis Athanasios 0000-0003-1677-4214 author Greisch Jean-Francois 0000-0002-0761-8191 author Papanastasiou Dimitrios author Gabelica Valérie 0000-0001-9496-0165 418070 Section des sciences pharmaceutiques (FARMA) 10.1101/2025.11.10.687689 http://biorxiv.org/lookup/doi/10.1101/2025.11.10.687689 We describe here various ion activation experiments realized in the Omnitrap platform integrated on the timsOmni mass spectrometer for the analysis of oligonucleotides in the negative ion mode. The activation methods include resonance collision-induced dissociation ( R CID), electron detachment dissociation (EDD), infrared laser multiple-photon activation (IRMPD) and UV laser photodissociation (UVPD). Special emphasis is given to EDD, either as a standalone technique or in conjunction with vibrational re-activation of the ion radicals. We describe EDD on standard 6-mer DNA sequences that have been extensively characterized on other instruments, followed by a comparison of several activation approaches for the phosphorothioate-based oligonucleotide therapeutics Fomivirsen, and concluding with the fragmentation analysis of 46-mer DNA and RNA. EDD alone already provides excellent sequence information on Fomivirsen, but MS 3 combinations such as EDD- R CID or EDD-IRMPD proved even more effective, including for the 46-mer DNA (less prone to fragmentation than RNA) at a relatively low charge state. The diversity of ion activation combinations available on the Omnitrap platform is demonstrated by an MS 4 experiment investigating the fate of a* and z* radical fragments produced by EDD. Déposé dans : bioRxiv Dewey 615 European Commission Ion Mobility Mass Spectrometry Training Network 101119562 MobiliTraIN EU HE Swiss National Science Foundation The Omnitrap platform coupled to a high-resolution mass spectrometer: a Swiss army knife to dissect complex molecular structures 220390 CH R'EQUIP 31 Section des sciences pharmaceutiques 17 false 1435 Spectrométrie de Masse Bio-Analytique (FASMA) 18477fce-86d2-4c3a-8f33-d35ee8b263d7 Preprint Public Preprint_maintext.pdf 1430005 application/pdf CC BY-4.0 a14dadb901c99e962a6ca66de6f6016547ca257be99e06762dbaeccd7bbb6234 323a4a97-799f-42cc-9e83-cba7677ab420 Supplemental data Public Preprint_supportinginfo.pdf 2398571 application/pdf CC BY-4.0 5e83c90068098e033667bd6c7002fac7b72bd54423935b2ff3342fffda051296 49a1e163-830a-4e43-94f2-4460247685b2 Supplemental data Public supplementary_Table_S7.xlsx 316499 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet CC BY-4.0 8f8ca15a1140ec36620513ff939d67232b2ec4f28c468373e520878d871fea91 0ef5b1dc-b5df-4977-96c4-ba39e1fa6d17 Supplemental data Public supplementary_Table_S8.xlsx 108165 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet CC BY-4.0 3475449069cc28cee1c88ab94f5ec6ed9ab886b02987516bf5163a1cdbcffcb6 Vignette Public TOC-graphics.jpg 122635 image/png openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Activation of oligonucleotide polyanions using collisions, electrons and photons in a timsOmni platform				2025	12	109

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Mani Mallika, Arjun