Mass spectrometry of G-quadruplex DNA: formation, recognition, property, conversion, and conformation

G-quadruplexes are special secondary structures formed from G-rich sequences of DNA, and have proven to play important roles in a number of biological systems, including the regulation of gene transcription and translation. The highly distinctive nature of G-quadruplex structures and their functions suggest that G-quadruplexes can act as novel targets for drug development. As a highly sensitive analytical tool, mass spectrometry has been widely used for the analysis of G-quadruplex structures. Electrospray-ionization mass spectrometry, in particular, has found captivating applications to probe interactions between small molecules and G-quadruplex DNA. In this review, we will discuss: (1) mass spectrometry probing of the formation, binding affinity, and stoichiometry between G-quadruplexes and small molecules; (2) stabilization and collision-dissociation behavior of G-quadruplex DNA; (3) the exploration of the equilibrium transfer between a G-quadruplex and duplex DNA; and (4) the ESI-MS analysis of the conversion of intramolecular and intermolecular G-quadruplexes. Finally, we will also introduce the application of new techniques in the analysis of G-quadruplex conformation, such as ion-mobility and infrared multiphoton-dissociation mass spectrometry. We believe that, with the new technical developments, mass spectrometry will play an unparalleled role in the analysis of the G-quadruplex structures.