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

1994; Wiley; Volume: 60; Issue: 4 Linguagem: Inglês

10.1111/j.1751-1097.1994.tb05110.x

1751-1097

Lidia Mastruzzo, Anne Woisard, D. F. David, Enrico Rizzarelli, Alain Favre, Trung Le Doan,

Porphyrin and Phthalocyanine Chemistry

Abstract 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 oligonucleotide‐porphyrin conjugates were tested for their ability to induce photodamage 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 exhibited a much higher cross‐linking yield than the methylpyrroporphyrin while the Zn‐porphyrin derivatives were found to be less efficient than their corresponding nonmetallated congeners. The specificity of the photocross‐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‐linking on the target RNA were identified at G residues located in close proximity to the porphyrin photoactive center in the hybrid and (3) addition of bulk calf liver RNA did not affect the photocross‐linking efficiency.