# Destabilizing Interactions in Human Telomeric G‑Quadruplex Multimers

**Authors:** Luca Bertini, Mattia Trapella, Deniz Mostarac, Valeria Libera, Caterina Petrillo, Cristiano De Michele, Lucia Comez, Alessandro Paciaroni

PMC · DOI: 10.1021/acs.jpclett.5c01100 · 2025-05-23

## TL;DR

This paper explores how G-Quadruplex structures in human telomeres interact and destabilize each other, affecting their arrangement and biological function.

## Contribution

The study introduces a helix–coil model to describe stacking–unstacking equilibrium in G-Quadruplex multimers using simulations and analytical methods.

## Key findings

- Significant destabilizing interactions between G-Quadruplexes reduce stacked conformations.
- A helix–coil model predicts stacked and unstacked G-Quadruplex multiplets in long sequences.

## Abstract

G-Quadruplexes are secondary structures that may form
in G-rich
nucleic acid sequences. The extended overhang at the ends of human
telomeres has the potential to form multiple G-Quadruplexes that are
crucial in regulating key biological processes. Here, we employ small-angle
X-ray scattering-guided extremely coarse-grained simulations to provide
a picture of the arrangement of G-Quadruplexes in long telomeric sequences.
We observe significant destabilizing interactions between G-Quadruplexes,
thus making the stacked conformation less prevalent. A helix–coil
model is proposed to analytically describe the stacking–unstacking
equilibrium within G-Quadruplex multimers and predict the occurrence
of stacked and unstacked G-Quadruplex multiplets in arbitrarily long
sequences.

## Full-text entities

- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12147199/full.md

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Source: https://tomesphere.com/paper/PMC12147199