Chlorin-Oligonucleotide Conjugates:  Synthesis, Properties, and Red Light-Induced Photochemical Sequence-Specific DNA Cleavage in Duplexes and Triplexes^,

Conjugates of oligonucleotides with chlorin-type photosensitizers were prepared. Two chlorin moieties, CPP and CHEVP, characterized by a modified pyrrole unit bearing an aldehyde chain, were photochemically prepared from protoporphyrin and heptaethylvinylporphyrin, respectively. These chlorin moieties were coupled through the carboxylic acid side-chain (CPP) or aldehyde side-chain (CHEVP) to the 3‘-activated phosphate of oligodeoxynucleotides. Diamine or dihydrazide were used as linkers. The resulting conjugates were purified by HPLC and characterized by electrophoresis, UV−visible spectroscopy, and mass spectrometry. The photosensitizing properties of the conjugate of CHEVP with the 14-mer oligodeoxynucleotide TTCTTCTCCTTTCT were investigated using three different targets. A single-stranded 25-mer containing the complementary sequence of the 14-mer formed a double helix with the chlorin-14-mer conjugate. A 24 base-pair duplex and a 41-mer hairpin with 18 base pairs and a five nucleotide loop formed tripl...