22/05/2026
Today Dr. David Monchaud (ICMUB, Dijon, France) has given a seminar at the IPBLN.
Titled: “Chemical Modulation of DNA/RNA G-Quadruplex (G4) Structures in Human Cells”.
Guanine (G)-rich DNA and RNA sequences can uniquely fold into structures known as G-quadruplexes (G4s). These four-stranded structures play key roles in DNA transactions (replication, transcription, repair) and genome stability. Over the past two decades, the field has evolved rapidly thanks to the development and use of small molecules—G4 ligands—designed to engage and probe G4s in cells. While thousands of ligands have been created, the ability to chemically destabilize them was long missing, precluding real chemical biology approaches. Surprisingly, the first hints of G4 destabilization came from TMPyP4—a molecule initially hailed as a G4 stabilizer. This study opened the way for new research into G4-unfolder molecules, culminating in PhpC, the most extensively studied destabilizer to date. PhpC has been shown to reshape DNA and RNA G4 landscapes in various cancer and neural cells, revealing the deep regulatory roles G4s play. This talk will explore the emergence of these molecules (referred to as molecular helicases) and their potential as both chemical biology tools and therapeutic agents in G4-linked diseases, including age-related disorders. The field now stands at an exciting turning point—where disrupting G4s may be just as powerful as stabilizing them.
