The G-quadruplex-forming telomeric sequence (TTAGGG)4TT was investigated by polarized Ultraviolet
Resonance Raman Scattering (UVRR) at 266 nm. The presence of 40% poly(ethylene glycol) and the so-called
‘‘self-crowding’’ condition were used to induce the hybrid-to-parallel topology transition. Analysis of frequency
shifts with temperature showed the role of several functional groups in the topological transitions and provides
structural dynamical information. Circular dichroism under similar conditions was used as a reference. UVRR
shed light on the effect of intramolecular interactions and of local and environmental dynamics in promoting
different G-quadruplex topologies, induced by solution conditions or by temperature changes. Overall, these
findings showed the enormous potential of this spectroscopy for G-quadruplex conformational studies.