G-quadruplex DNA cleavage preference and identification of a perylene diimide G-quadruplex photocleavage agent using a rapid fluorescent assay

Abstract

A rapid fluorescence assay for G-quadruplex DNA cleavage was used to investigate the preference of TMPyP4 photochemical and Mn·TMPyP4 oxidative cleavage. Both agents most efficiently cleave the c-Myc promoter G-quadruplex. Direct PAGE analysis of selected assay samples showed that for a given cleavage agent, different cleavage products are formed from different G-quadruplex structures. Cleavage assays carried out in the presence of excess competitor nucleic acid structures revealed the binding selectivity of cleavage agents, while comparisons with duplex cleavage efficiency employing a dual-labeled hairpin oligonucleotide revealed neither agent prefers G-quadruplex over duplex substrates. Finally, this assay was used to identify the perylene diimide Tel11 as a photocleavage agent for the c-Myc G-quadruplex.