0_3169 Nucleic acid sequences rich in guanines can organize into noncanonical DNA G-quadruplexes (G4s) of variable size. The high degree of polymorphism together with conformational switching properties enables the structural reconfiguration of G4s and promotes their applications in sensing, analytical biochemistry, and logic gate development. In this context, the design of small molecules stabilizing the structure of G4s is a rapidly growing area for the development of novel anticancer therapeutic strategies and bottom-up nanotechnologies. Here, we adopted an integrated experimental approach to study the structural and thermodynamic properties of the G4 formed by a human telomeric 22-mer sequence (Tel22) in the presence of model drugs, upon thermal unfolding or irradiation with visible light [1-3]. Singular value decomposition analysis applied to circular dichroism and resonant Raman scattering spectra allowed us to identify a temperature region populated with intermediate conformers along the path from the native to the unfolded state, for both the quadruplex alone and the complexes. The attitude of telomeric sequences to form multimers was also studied by using a novel low-resolution structural approach that combine Small Angle X-ray Scattering (SAXS) with extremely coarse-grained (ECG) simulations. This integrated approach has proven to be effective in determining the degree of multimerization and the strength of the stacking interaction in G4 aggregates [4]. [1] F. Bianchi, L. Comez*, R. Biehl, F. D’Amico, A. Gessini, M. Longo, C. Masciovecchio, C. Petrillo, A. Radulescu, B. Rossi, F. Sacchetti, F. Sebastiani, N. Violini, A. Paciaroni, Nucleic Acids Research, 46, 11927-11938, 2018; DOI: 10.1093/nar/gky1092.[2] V. Libera, E.A. Andreeva, A. Martel, A. Thureau, M. Longo, C. Petrillo, A. Paciaroni, L. Comez*, The Journal of Physical Chemistry Letters 12 (33), 8096-8102, 2021; DOI:10.1021/acs.jpclett.1c01840.[3] V Libera, F Bianchi, B Rossi, F D’Amico, C Masciovecchio, C Petrillo, F. Sacchetti, A. Paciaroni, L. Comez, International Journal of Molecular Sciences 23 (9), 5123, 2022, DOI: 10.3390/ijms23095123.[4] B.P. Rosi et al. arXiv preprint arXiv:2203.06521.