TARGETED PHOTOCHEMICAL MODIFICATION OF HIV-DERIVED OLIGORIBONUCLEOTIDES BY ANTISENSE OLIGODEOXYNUCLEOTIDES LINKED TO PORPHYRINS

Antisense oligodeoxynucleotides directed against a 24-mer RNA derived from the long terminal repeat (LTR) region of HIV were linked to proto - and methylpyrroporphyrin and their zinc derivatives. The oligonucleo tide-porphyrin conjugates were tested for their ability to induce phot odamage on the target RNA. Upon hybridization followed by irradiation at 405 nm, the photochemical reaction led to photocross-linking of the antisense derivative to the RNA substrate. The protoporphyrin exhibit ed a much higher cross-linking yield than the methylpyrroporphyrin whi le the Zn-porphyrin derivatives were found to be less efficient than t heir corresponding nonmetallated congeners. The specificity of the pho tocross-linking reaction between the porphyrin-oligomer and its target RNA was demonstrated by the following evidence: (1) hybrid formation was required for photocross-linking to occur, (2) the sites of cross-l inking on the target RNA were identified at G residues located in clos e proximity to the porphyrin photoactive center in the hybrid and (3) addition of bulk calf liver RNA did not affect the photocross-linking efficiency.