Small-molecule quadruplex-targeted drug discovery.

Repeated guanine tracts in human and other genomes can form higher-order four stranded structures, termed quadruplexes. In the human genome they have particular prevalence in telomeric and promoter regions and also in 5'-UTRs and introns. These structures, if unresolved and stabilised by small molecules, can form impediments to transcription and translation, and thus can be considered as a form of gene targeting. This Digest surveys the major types of quadruplex-binding small molecules that have been designed and studied to date and directs attention to directions where future development of more drug-like compounds is likely to be most productive.