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Nucleic Acids Research, 1992, Vol. 20, No. 10 2421-2426
© 1992


CHEMISTRY

Chemical synthesis of 2'-deoxyoligonucleotides containing 5-fluoro-2'-deoxycytidine

Sabine Schmidt, Claus-Dietmar Pein+, Hans-Joachim Fritz1,* and Dieter Cech

Institut für Bioorganische Chemie, Humboldt-Universität zu Berlin Invalidenstraße 42, O-1040 Berlin 1Institut für Molekulare Genetik, Georg-August-Universität Göttingen Grisebachstraße 8, W-3400 Göttingen, Germany

* To whom correspondence should be addressed

Received April 8, 1992. Accepted April 22, 1992.

2'-Deoxyoligonucleotides with 5-fluorocytosine residues incorporated at specific positions of the nucleotide sequence are tools of great potential in the study of the catalytic mechanism by which DNA cytosine methyltransferases methylate the 5-position of DNA cytosine residues in specific sequence contexts. Chemical synthesis of such oligonucleotides is described. Two alternative approaches have been developed, one of which proceeds via a fully protected phosphoramidite of 5-fluoro-4-methylmercapto-2'-deoxyuridine 2, the other via a fully protected phosphoramidite of 5-fluoro-2'-deoxycytidine 3. Either building block can be used in automated oligonucleotide synthesis applying standard elongation cycles and deprotection procedures exclusively. The methylmercapto function of 2 is replaced by an amino group in the final ammonia treatment used for cleavage from support and base deprotection.


+ Present address: Pharmacia Biosystems GmbH, Munzinger Straße 9, W-7800 Freiburg, Germany


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