Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1995-05-22
1998-12-08
Kunz, Gary L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 2431, 536 2432, 536 231, C07H 2100, C07H 2102, C07H 2104
Patent
active
058471049
ABSTRACT:
The present invention comprises a novel method of incorporating a tritium label at one or more predetermined sites within an oligonucleotide. In particular, the method comprises contacting a nascent, support-bound oligonucleotide having a free 5' hydroxyl group with a suitable oxidizing agent to oxidize the alcohol to an aldehyde, followed by reducing the aldehyde thereby formed with a suitable tritium labeled reducing agent tritium label. Normal automated synthesis can then be continued to yield the oligonucleotide of desired length having the tritium label in the desired location. The oligonucleotides thereby produced have higher specific activity than those previously known in the art. According, in a second aspect, the present invention provides oligonucleotides having high specific acitivity. The oligonucleotides of the present invention are useful for determining the pharmacokinetics and biodistribution of their non-radiolabeled counterparts, both in vitro and in vivo.
REFERENCES:
Graham et al. Nucl. Acids Res. 21: 3737, 1993.
Agrawal and Tang, Antisense Res. And Dev. 2, 261-266 (1992).
Agrawal et al., Clin. Pharmacokinet. 28, 7-16 (1995).
Agrawal et al., Proc. Natl. Acad. Sci USA 88, 7596-7599 (1991).
Agrawal, TIBETCH 10, 152-158 (1992).
Albright and Goldman, J. Am. Chem. Soc. 87, 4214-4216 (1965).
Bayever et al., Antisense Res. And Dev. 3, 383-390 (1993).
Beaucage and Caruthers, Tetrahedron Lett. 22, 1859-1862 (1981).
Berger et al., Nucleosides and Nucleotides 6, 395-396 (1987).
Breter et al., Chemical Abstracts 91 (25), p. 274, col. 2 (1979).
Dess and Martin, J. Am. Chem. Soc. 113, 7277-7287 (1991).
Dess and Martin, J. Org. Chem. 48, 4155-4156 (1983).
Garegg et al., Chemica Scripta 25, 280-282 (1985).
Graham et al., Nucleic Acids Res. 21, 3737-3743 (1993).
House, Modern Synthetic Reactions, Chapter 2, pp. 23-49 (W.A. Benjamin Inc., New York, 1965).
Jones and Moffatt, Methods in Carbohydrate Chemistry, vol. 6, pp. 315-322 (1972).
Ling et al., Chemical Abstracts 122 (13), p. 427, col. 2 (1995).
March, Advanced Organic Chemistry: Reactions and Mechanisms, pp. 809-814 (Third Ed., John Wiley & Sons, 1985).
Onodera et al., Carbohydrate Research 6, 276-285 (1968).
Parikh and von E. Doehring, J. Am. Chem. Soc. 89, 5505-5507 (1967).
Pfitzner and Moffatt, J. Am. Chem. Soc. 87, 5661-5770 (1965).
Sambrook et al., Molecular Cloning: A Laboratory Manual, 2.sup.nd Ed., Cold Spring Harbor Laboratory Press, 7.37-7.52 (1989).
Sasmor et al., J. Labeled Compd. And Radiopharm. 36, 15-31 (1995).
Southern, J. Mol. Biol. 98, 503-517 (1975).
Stein and Cheng, Science 261, 1004-1012 (1993).
Agrawal Sudhir
Iyer Radhakrishnan P.
Jiang Zhiwei
Tan Weitan
Yu Dong
Hybridon, Inc.
Kunz Gary L.
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