Building on an Innovative Platform: Tuning Guanine Quadruplex Recognition for Anticancer Applications
Beyond the well-known double-stranded helical duplex, DNA can adopt many unusual architectures, including guanine quadruplexes (G4), which in recent years have been implicated in cellular processes that lead to the development of cancer. It has been shown that these processes can be switched off by maintaining the folded quadruplex architecture using chemical compounds known as G4 binders. Good G4 binders can be identified by screening a large number of candidates using high-throughput techniques such as the one pioneered by the Mergny research group at the Institut Européen de Chimie et Biologie in France, which rapidly provides a yes/no outcome. With the support of Mitacs Globalink Research Award – Campus France funding, I could not only screen a library of second-generation G4 binders synthesized in the Petitjean lab, but also conduct a range of experiments to determine (i) the selectivity of these binders for quadruplex vs. duplex DNA, (ii) the binding strength and number of binders to G4 involved in binding events, and (iii) the structural aspects involved in G4 binding. With the expected outcomes of this research, we aim to lay the groundwork for the commercialization of a novel G4 binder for clinical use in targeted anticancer therapies.