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Wiley, Angewandte Chemie International Edition, 3(54), p. 910-913, 2014

DOI: 10.1002/anie.201408113

Wiley, Angewandte Chemie, 3(127), p. 924-927, 2014

DOI: 10.1002/ange.201408113

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Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G-Quadruplex**

Journal article published in 2014 by Philip M. Yangyuoru, Marco Di Antonio ORCID, Chiran Ghimire, Giulia Biffi ORCID, Shankar Balasubramanian, Hanbin Mao
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This paper is available in a repository.

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Abstract

In investigating the binding interactions between the human telomeric RNA (TERRA) G-quadruplex (GQ) and its ligands, it was found that the small molecule carboxypyridostatin (cPDS) and the GQ-selective antibody BG4 simultaneously bind the TERRA GQ. We previously showed that the overall binding affinity of BG4 for RNA GQs is not significantly affected in the presence of cPDS. However, single-molecule mechanical unfolding experiments revealed a population (48 %) with substantially increased mechanical and thermodynamic stability. Force-jump kinetic investigations suggested competitive binding of cPDS and BG4 to the TERRA GQ. Following this, the two bound ligands slowly rearrange, thereby leading to the minor population with increased stability. Given the relevance of G-quadruplexes in the regulation of biological processes, we anticipate that the unprecedented conformational rearrangement observed in the TERRA-GQ–ligand complex may inspire new strategies for the selective stabilization of G-quadruplexes in cells.