Thiazole orange-conjugated peptide nucleic acid for fluorescent detection of specific DNA sequences and site-selective photodamage

Abstract

A fluorescent probe to detect specific sequences in double-stranded DNA (dsDNA) has been synthesized by conjugating thiazole orange (TO) with pseudo-complementary peptide nucleic acid (pcPNA). A pair of TO-conjugated pcPNAs bound to the target site in dsDNA through double-duplex invasion, and promoted intercalation of the TO moieties for notable enhancement of their fluorescence. Site-specificity of the detection is high enough to differentiate only one base-pair difference in DNA. These TO-pcPNA conjugates also function as site-selective photo-damage inducers. Upon irradiation with visible light, singlet oxygen was generated by energy transfer from the dyes at the invasion site, resulting in the site-selective formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxoG) there.