Stabilization of G-Quadruplex DNA by Highly Selective Ligands via Click Chemistry

摘要

The telomeres of eukaryotic species comprise specialized protein-DNA complexes that protect chromosome ends,ensuring that end-to-end fusions,recombination,or damage do not occur.1 These involve tandem repeats of guanine-rich DNA sequences,typified by [TTAGGG]in vertebrates.There are fundamental differences between telomere maintenance in somatic compared to cancer cells,which may be exploitable therapeutically.The progressive shortening of telomeres in the former eventually leads to senescence and apoptosis.Telomeres in cancer cells,by contrast,are stabilized in length,in the overwhelming majority of tumors by the activation of the telomerase enzyme complex,which has reverse transcriptase activity such that it is able to catalyze the synthesis of further telomere repeats onto the 3'single-stranded end of telomeres.