Influence of Modifications of the Structure and Stability of Guanosine Nucleoside Analogues: Studies using Complementary Spectroscopic, Mass Spectrometric, and Electronic Structure Theory Approaches

As fundamental building blocks of nucleic acids, nucleosides play important roles in the molecular biology of all living organisms. Their involvement in DNA replication, transcription, and translation is essential for the storage and expression of genetic information. Nucleosides also play roles in cellular signaling and metabolism. To facilitate these varied functions, nucleosides are subject to naturally occurring post-transcriptional modifications that provide evolutionary advantages. In contrast, oxidative stress or chemical exposure can also lead to nucleoside modifications that may negatively impact health and can lead to various disease states. As a result, nucleoside modifications have been widely studied, used for diagnostic assays, and have been employed in the development of drugs for various therapeutic applications. In this work, complementary tandem mass spectrometry approaches (infrared multiple photon dissociation action spectroscopy and energy-resolved collision-induced dissociation experiments) and electronic structure theory calculations are employed to examine the effects of various naturally occurring and synthetic modifications of the guanine nucleobase and sugar moieties on the structure and glycosidic bond stability of guanosine nucleoside analogues. Comparisons are made to the canonical DNA and RNA guanosine nucleosides as well as related modified nucleoside analogues to elucidate the effects of the modifications.