Solvent Vibrations as a Proxy of the Telomere G-Quadruplex Rearrangements across Thermal Unfolding

Abstract

G-quadruplexes (G4s) are noncanonical forms of DNA involved in many key genome functions. Here, we exploited UV Resonance Raman scattering to simultaneously explore the vibrational behavior of a human telomeric G4 (Tel22) and its aqueous solvent as the biomolecule underwent thermal melting. We found that the OH stretching band, related to the local hydrogen-bonded network of a water molecule, was in strict relation with the vibrational features of the G4 structure as a function of temperature. In particular, the modifications to the tetrahedral ordering of the water network were strongly coupled to the DNA rearrangements, showing changes in temperature that mirrored the multi-step melting process of Tel22. The comparison between circular dichroism and Raman results supported this view. The present findings provide novel insights into the impact of the molecular environment on G4 conformation. Improving current knowledge on the solvent structural properties will also contribute to a better understanding of the role played by water arrangement in the complexation of G4s with ligands.

Stability of Human Telomeric G-Quadruplexes Complexed with Photosensitive Ligands and Irradiated with Visible Light

“…The present work is focused on human telomeric G4s, formed by tandem repeats of the sequence d(TTAGGG), which have been revealed in vivo in the terminal part of chromosomes [8]. Among them, we selected the AG3(TTAG3)3 (Tel22) sequence, which can exist in vitro as parallel, hybrid-3+1, antiparallel, and two-tetrad antiparallel (hybrid-3) structures [23][24][25][26][27][28][29], depending on various ionic and crowding conditions. Based on past literature, it appears that hybrid-type telomere conformations are the most physiologically and thermodynamically relevant [30].…”

Role of fast dynamics in the complexation of G-quadruplexes with small molecules

“…5,6 In addition, also the arrangement of the water network surrounding G4s may have a significant impact on their conformational properties. 7 Because of their polymorphism, G4s display an elusive and transient character, which is also the main reason why they were discovered in vivo only very recently. 8 A schematic representation of different architectures for intramolecular G4s is shown in Fig.…”

Chemistry and Biology of Noncanonical Nucleic Acid Structures: From Physicochemical Properties to Therapeutic Applications

“…Libera et al utilized UV resonance Raman scattering to explore the vibrational behavior of a human telomeric G-quadruplex and its aqueous solvent during the thermal denaturation of the DNA molecule [20]. The results revealed that in aqueous G-quadruplex solutions, as in canonical B-DNA, the solute-solvent interactions detected by Raman spectroscopy are mutual.…”