Antisense sequence-directed cross-linking of RNA oligonucleotides by mitomycin

Helena Maruenda, Maria Tomasz

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

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Conjugates of mitomycin C (MC) and 15-mer oligodeoxyribonucleotides (ODNs) were synthesized in which the 7-amino group of MC was tethered by either a (-CH2-)6 or a (-CH2-)12 linker to the 5'-terminal phosphate of the ODNs. The conjugates were shown to be cross-linked selectively to complementary 18-mer oligoribonucleotides (ORNs). The cross-linking was dependent on reductive activation of the MC moiety of the conjugates by NADPH-cytochrome c reductase/NADPH. The cross-linked ODN-ORN hybrid duplexes were characterized as such by degeneration by RNase H. Cross-linking efficiencies of the conjugates were 50 and 25% in the case of the (-CH2-)12 tether and the (-CH2-)6 tether respectively. The results demonstrate the feasibility of sequence-targeted alkylation of RNA by MC via antisense recognition.

Idioma originalInglés
Páginas (desde-hasta)473-479
Número de páginas7
PublicaciónAnti-Cancer Drug Design
EstadoPublicada - set. 1997


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