Molecular Mechanisms Behind Braco19 and Human Telomeric Gquadruplex Interaction

27 Pages Posted: 23 Apr 2024

See all articles by valeria libera

valeria libera

University of Perugia

Claudia Fasolato

affiliation not provided to SSRN

Francesca Ripanti

Polytechnic University of Marche

Sara Catalini

University of Perugia

Luca Bertini

University of Perugia

Caterina Petrillo

University of Perugia

Francesco D’Amico

affiliation not provided to SSRN

Barbara Rossi

affiliation not provided to SSRN

alessandro paciaroni

University of Perugia

lucia comez

affiliation not provided to SSRN

Abstract

Human telomeres (HTs) can form DNA G-quadruplex (G4), an attractive target for anticancer and antiviral drugs. HT-G4s exhibit inherent structural polymorphism, posing challenges for understanding their specific recognition by ligands. Here, we aim to explore the impact of different topologies within a small segment of the HT (Tel22) on its interaction with BRACO19, a rationally designed G4 ligand with high quadruplex affinity, already employed in in vivo treatments. Our multi-technique approach is based on the combined use of a set of contactless spectroscopic tools. Circular dichroism and UV resonance Raman spectroscopy probe ligand-induced conformational changes in the G4 sequence, while UV-visible absorption, coupled with steady-state fluorescence spectroscopy, provides further insights into the electronic features of the complex, exploiting the photoresponsive properties of BRACO19. Overall, we find that modifying the topology of the unbound Tel22 through cations (K+ or Na+), serves as a critical determinant for ligand interactions and binding modes, thus influencing the HT-G4’s assembly capabilities. Furthermore, we show how fluorescence serves as a valuable probe for recognizing cation-driven multimeric structures, which may be present in living organisms, giving rise to pathological forms.

Keywords: G-quadruplex, BRACO19, biophysical approach

Suggested Citation

libera, valeria and Fasolato, Claudia and Ripanti, Francesca and Catalini, Sara and Bertini, Luca and Petrillo, Caterina and D’Amico, Francesco and Rossi, Barbara and paciaroni, alessandro and comez, lucia, Molecular Mechanisms Behind Braco19 and Human Telomeric Gquadruplex Interaction. Available at SSRN: https://ssrn.com/abstract=4799542 or http://dx.doi.org/10.2139/ssrn.4799542

Valeria Libera (Contact Author)

University of Perugia ( email )

Via Pascoli 22
Perigoa, 06121
Italy

Claudia Fasolato

affiliation not provided to SSRN ( email )

No Address Available

Francesca Ripanti

Polytechnic University of Marche ( email )

Piazzale Martelli 8
Ancona, 18039
Italy

Sara Catalini

University of Perugia ( email )

Via Pascoli 22
Perigoa, 06121
Italy

Luca Bertini

University of Perugia ( email )

Via Pascoli 22
Perigoa, 06121
Italy

Caterina Petrillo

University of Perugia ( email )

Via Pascoli 22
Perigoa, 06121
Italy

Francesco D’Amico

affiliation not provided to SSRN ( email )

No Address Available

Barbara Rossi

affiliation not provided to SSRN ( email )

No Address Available

Alessandro Paciaroni

University of Perugia ( email )

Via Pascoli 22
Perigoa, 06121
Italy

Lucia Comez

affiliation not provided to SSRN ( email )

No Address Available

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