G-quadruplex structural transition driven by a platinum compound

G-quadruplex (G4) transitions play integral roles in regulating biological functions and can be modified by ligands. However, little is known about G4 transitions. Herein, we reveal distinct pathways of a platinum(II) compound Pt-phen converting parallel-stranded MYC G4 to a hybrid-type structure. Three NMR structures, 1:1 5 '-end binding, 1:1 3 '-end binding and 2:1 Pt-phen-MYC G4 complexes, were determined by NMR. We find that Pt-phen drives G4 transition at a low ratio. Under physiological 100 mM K+ conditions, a significant stable hydrogen-bonded T:T:A triad is formed at 3 '-end of hybrid-type Myc1234, and consequently, Pt-phen first binds the 5 '-end to form a 1:1 5 '-end binding complex and then disrupts the 3 ' T:T:A triad and binds 3 '-end to form a 2:1 complex with more Pt-phen. Remarkably, the G4 transition pathway is different in 5 mM K+ with Pt-phen first binding the 3 '-end and then the 5 '-end. 'Edgewise-loop and flanking/ligand/G-tetrad' sandwich structure formation and terminal T:T:A triad stabilization play decisive roles in advancing and altering transition pathways. Our work is the first to elucidate the molecular structures of G4 transitions driven by a small molecule. The ligand-driven G4 transition is a dynamic process that includes a quick G4 transition and multiple complexes formation.

Automated summary

This study elucidates the pathways of G4 transitions driven by a platinum(II) compound Pt-phen. The formation of complexes differs under physiological conditions compared to low potassium ion conditions. The results demonstrate the crucial role of Pt-phen binding sites in the G4 transition process.