Antisense sequence-directed cross-linking of DNA oligonucleotides by mitomycin C.
1996
Oligodeoxyribonucleotides (ODNs) conjugated with mitomycin C (MC) via (−CH2−)n tethers of different lengths (n = 6, 12) to their terminal 5‘-phosphate were synthesized, and their interaction with target complementary single-stranded DNA oligonucleotides was investigated. MC, a clinically used natural anticancer drug, is known to act as a bioreductive alkylating agent of duplex DNA with a remarkable preference for 5‘-d(CG) sequences. The usual enzymatic bioreductive techniques known to trigger MC to alkylate DNA were employed in the reaction between the MC−oligonucleotide conjugates and their targets radiolabeled by 32P at their 5‘-phosphate. A slow-moving radiolabeled product, detected by polyacrylamide gel electrophoresis using phosphorimaging techniques, was obtained in 15−25% yield with complementary DNA as target. Formation of these products was dependent upon complementary duplex formation. Evidence is presented that the DNA target is alkylated by the mitomycin C moiety of the ODN conjugate at the 2-...
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
7
References
10
Citations
NaN
KQI