The widespread of G-quadruplex-forming sequences in genomic DNA and their role in regulating gene expression has made G-quadruplex structures attractive therapeutic targets against a variety of diseases, such as cancer. Information on the structure of G-quadruplexes is crucial for understanding their physiological roles and designing effective drugs against them. Resolving the structures of G-quadruplexes, however, remains a challenge especially for those in double-stranded DNA. In this work, we developed a photocleavagefootprinting technique to determine the foldingorientation of each individual G-tract in intramolecular G-quadruplex formed in both single- and double-strandednucleicacids. Based on the differential photocleavage induced by a ligand tetrakis(2-trimethylaminoethylethanol) phthalocyaninato zinc tetraiodine (Zn-TTAPc) to the guanines between the two terminal G-quartets in a G-quadruplex, this method identifies the guanines hosted in each terminal G-quartets to reveal G-tractorientation. The method is extremely intuitive, straightforward, and requires little expertise. Besides, it also detects G-quadruplex formation in longsingle- and double-strandednucleicacids.

Zheng K, Zhang D, Zhang L, Hao Y, Zhou X, Tan Z*. (2011) Dissecting the strand folding orientation and formation of G-quadruplexes in single- and double-stranded nucleic acids by ligand-induced photocleavage footprinting. J Am Chem Soc. , 133(5):1475-1483.