Synthesis of macrocyclic hexaoxazole (6OTD) dimers, containing guanidine and amine functionalized side chains, and an evaluation of their telomeric G4 stabilizing properties

Abstract

Structure-activity relationship studies were carried out on macrocyclic hexaoxazole (6OTD) dimers, whose core structure stabilizes telomeric G-quadruplexes (G4). Two new 6OTD dimers having side chain amine and guanidine functional groups were synthesized and evaluated for their stabilizing ability against a telomeric G4 DNA sequence. The results show that the 6OTD dimers interact with the DNA to form 1:1 complexes and stabilize the antiparallel G4 structure of DNA in the presence of potassium cation. The guanidine functionalized dimer displays a potent stabilizing ability of the G4 structure, as determined by using a FRET melting assay (Δ Tm =14°C). Copyright © 2010 Keisuke Iida et al.