Regiospecific inhibition of DNA duplication by antisense phosphate-methylated oligodeoxynucleotides. |
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Authors: | H M Moody M H van Genderen L H Koole H J Kocken E M Meijer and H M Buck |
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Institution: | Department of Organic Chemistry, Eindhoven University of Technology, The Netherlands. |
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Abstract: | A new synthesis route for long phosphate-methylated oligodeoxynucleotides is described, which were used as antisense inhibitors of the DNA replication. Phosphate-methylated oligomers hybridize more strongly with natural DNA than their natural analogues, due to the absence of electrostatic interstrand repulsions. Compared with phosphate-ethylated and methyl phosphonate systems, phosphate-methylated systems are preferable as antisense DNA, which was concluded from the high Tm values and sharp melting transitions of duplexes of phosphate-methylated and natural DNA. By using the Sanger dideoxy technique, it was shown that a complementary phosphate-methylated 18-mer can effectively and site-specifically block the DNA replication process at room temperature. |
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