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pubmed-article:8889014pubmed:dateCreated1997-2-4lld:pubmed
pubmed-article:8889014pubmed:abstractTextOligodeoxyribonucleotides (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-amino group of a guanine base. These findings suggest that the MC-ODN conjugates may be useful specific inhibitors of cellular or viral gene expression. To our knowledge this is the first report on ODN conjugates of a reductively activated drug of known therapeutic value.lld:pubmed
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pubmed-article:8889014pubmed:authorpubmed-author:TomaszMMlld:pubmed
pubmed-article:8889014pubmed:authorpubmed-author:MaruendaHHlld:pubmed
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pubmed-article:8889014pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:8889014pubmed:articleTitleAntisense sequence-directed cross-linking of DNA oligonucleotides by mitomycin C.lld:pubmed
pubmed-article:8889014pubmed:affiliationDepartment of Chemistry, Hunter College, City University of New York, New York 10021, USA.lld:pubmed
pubmed-article:8889014pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:8889014pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed