title: Utilizing G-quadruplex formation to target 8-oxoguanine in telomeric sequences.
abstract: Utilizing G-quadruplex specific ligands that can induce/bind G-quadruplex DNA in human telomeric regions has recently become an attractive means for cancer chemotherapy because the formation of G-quadruplex structures inhibits the activity of telomerase, a reverse transcriptase mainly expressed in cancer cells. In the present work, we synthesized a type of bifunctional molecules that selectively bind to telomeric DNA via G-quadruplex formation and subsequently react with proximate OxodG in the presence of one-electron oxidant. Such molecules could be useful for telomerase inhibition. Perylene derivatives (7 and 9) containing 1,3-diamino moieties were prepared for demonstration. The binding of 7 with G-quadruplex DNA was determined using UV thermal denaturation and the corresponding binding constant was derived from UV titration. The interactions of 7 with G-quadruplex DNA containing OxodG were characterized using circular dichroism. Gel electrophoresis revealed that 7 can form more adducts with OxodG in G-quadruplex regions than that in duplex DNA.
authors.affiliation: Department of Chemistry, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Chitranshi
authors.forename: Liang
authors.initials: L
authors.lastname: Xue
mesh_terms: D002942:Circular Dichroism; D054856:G-Quadruplexes; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D016615:Telomere
chemical_list: C024829:8-hydroxyguanine; D006147:Guanine