The team led by Prof. Yves MELY, with Pankhi Singh and Dipanjan Mukherjee as first authors, has just published a major study in the field of structural biology. Their work reveals how thienoguanosine (thG), a fluorescent isomorphic analog of guanosine, enables the exploration of the structure and dynamics of hTel22—a human telomeric G-quadruplex (G4) sequence—with unprecedented precision.
G-quadruplexes play a key role in gene regulation and represent promising targets for drug development, particularly in oncology. Until now, their dynamic study has remained challenging due to their structural complexity.
Using the thG, the team was able to:
- Preserve the native antiparallel structure of hTel22 and its thermal stability (in Na buffer) when substituting guanines in the outer tetrads.
- Promote the antiparallel topology in K buffer, with slight destabilization.
- Show that thG is highly emissive and sensitive to its local environment in external tetrads
- Characterize in real time and high precision the Na-induced G4 folding kinetics.
- Achieve an exceptional signal-to-noise ratio: the fluorescence lifetime of thG is 2 to 3 times longer than that of DNA duplexes, which allows clear distinction between G4 and duplexes.
This breakthrough paves the way for drug screening targeting G4s, dynamic studies of nucleic acids, and anticancer therapy research.
Congratulations to the entire team and their collaborators!
