Sequence-targeted chemical modifications of nucleic acids by complementary oligonucleotides covalently linked to porphyrins.
Oligo-heptathymidylates covalently linked to porphyrins bind to complementary sequences and can induce local damages on the target molecule. In dark reactions, iron porphyrin derivatives exhibited various chemical reactivities resulting in base oxidation, crosslinking and chain scission reactions. Reactions induced by reductants, such as ascorbic acid, dithiothreitol or mercapto-propionic acid, led to very localised reactions. A single base was the target for more than 50% of the damages. Oxidising agents such as H2O2 and its alkyl derivatives induced reactions that extended to a wider range of altered bases. The specificity of the chemical modifications observed in these systems is discussed from a mechanistic point of view.
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U.201, Paris, France.
Trung Le Doan
L
L
Perrouault
M
M
Chassignol
T T
TT
Nguyen
C
C
Hélène
D000477:Alkylating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000585:Aminacrine / Q000031:analogs & derivatives / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000494:pharmacology*; D004249:DNA Damage; D004229:Dithiothreitol / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008665:Metalloporphyrins / Q000378:metabolism / Q000494:pharmacology*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D011071:Poly T / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D000477:Alkylating Agents; D003432:Cross-Linking Reagents; D008665:Metalloporphyrins; D011089:Polydeoxyribonucleotides; D013438:Sulfhydryl Compounds; D009243:NAD; D011071:Poly T; D000585:Aminacrine; D006861:Hydrogen Peroxide; C023884:thiolactic acid; D001205:Ascorbic Acid; D004229:Dithiothreitol