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 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.
Mastruzzo
L
L
Laboratoire de Chimie, CNRS URA 401, Paris, France.
Woisard
A
A
Ma
D D
DD
Rizzarelli
E
E
Favre
A
A
Le Doan
T
T
D001483:Base Sequence; D017931:DNA Primers; D006678:HIV / Q000235:genetics*; D016325:HIV Long Terminal Repeat; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D009843:Oligoribonucleotides / Q000737:chemistry* / Q000528:radiation effects; D010777:Photochemistry; D011166:Porphyrins; D012367:RNA, Viral / Q000235:genetics
D017931:DNA Primers; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D009843:Oligoribonucleotides; D011166:Porphyrins; D012367:RNA, Viral