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Title: Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer. Author: Neidle S. Journal: FEBS J; 2010 Mar; 277(5):1118-25. PubMed ID: 19951354. Abstract: The 3'-ends of human chromosomal DNA terminate in short single-stranded guanine-rich tandem-repeat sequences. In cancer cells, these are associated with the telomere-maintenance enzyme telomerase together with the end-binding protein hPOT1. Small molecules that can compete with these proteins and induce the single-stranded DNA to form quadruplex-ligand complexes are, in effect, able to expose these 3'-ends, which results in the activation of a DNA damage response and selective inhibition of cell growth. Several of these G-quadruplex binding molecules have shown promising anticancer activity in tumour xenograft models, which indicate that the approach may be applicable to the treatment of a wide range of human cancers. This minireview summarizes the available data on these compounds and the challenges posed for drug discovery.[Abstract] [Full Text] [Related] [New Search]