Triarylpyridines: a versatile small molecule scaffold for G-quadruplex recognition

摘要

The triarylpyridines are potent G-quadruplex ligands that are highly discriminating against duplex DNA and show promising selectivity between intramolecular quadruplexes. G-Quadruplexes are nucleic acid secondary structures formed from guanine-rich sequences, and comprise a planar arrangement of four guanines (G-tetrad) stabilised by Hoogsteen hydrogen bonding and monovalent cations. Putative quad-ruplex forming sequences have been identified throughout the genome, raising the possibility of function. The best-studied example is that of the human telomeric quadruplex, whose stabilisation by a small molecule leads to the inhibition of telomerase activity and interference with telomere biology. Quadruplex motifs are enriched in gene promoters, which is suggestive of their involvement in gene transcription. Promoter quadruplexes have been studied for several proto-onco-genes that include c-myc, VEGF, bcl-2, KRAS and c-kit.