Lysinyl macrocyclic hexaoxazoles: Synthesis and selective G-quadruplex stabilizing properties

Macrocyclic hexaoxazoles having one or two lysinyl side chains in which the terminal nitrogen is either a primary amine, N,N-dimethylamine, or an acetamide have been synthesized. Sodium ion has been found to be beneficial to the macrocyclization step by acting as a template around which the linear polyoxazole can organize. Each of the targeted compounds selectivity stabilizes G-quadruplex versus duplex DNA. Compounds with one valine and one lysine residue display the best combination of G-quadruplex stabilizing ability with no detectable stabilization of duplex DNA.

Graphical abstractThe synthesis of 24-membered macrocyclic hexaoxazoles incorporating one or two lysine residues is reported. Each compound was evaluated for selective stabilization of G-quadruplex DNA.Figure optionsDownload full-size imageDownload as PowerPoint slide