Method of tritium labeling oligonucleotides

Details Method of tritium labeling oligonucleotides Method of tritium labeling oligonucleotides

1995-06-07

1997-09-16

Jones, W. Gary

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 253, C07H 1900, C07H 2100, C07H 2102, C07H 2104

Patent

active

056682620

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 such as [.sup.3 H]NaBH.sub.4 to yield the 5' terminal alcohol with a 5' 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 activity. 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:
patent: 4521592 (1985-06-01), Dahmen et al.
Bayever et al., Antisense Res. and Dev. 3, 383 (1993).
Garegg et al., Chemica Scripta 25, 280-282 (1985).
Sasmor et al., J. Labeled Compd. and Radiopharm. 36, 15-31 (1995).
Onodera et al., Carbohydrate Research 6, 276 (1968).
Parikh and von E. Doehring, J. Am. Chem. Soc. 89, 5505 (1967).
Dess and Martin, J. Org. Chem. 48, 4155 (1983).
House, Modern Synthetic Reactions, Chapter 2, pp. 23-49 (W.A. Benjamin Inc., New York. 1965).
March, Advanced Organic Chemistry: Reactions and Mechanisms, pp. 809-814 (Third Ed., John Wiley & Sons. 1985).
Agrawal, TIBTECH 10, 152-158 (1992).
Stein and Cheng, Science 261, 1004 (1993).
Agrawal and Tang, Antisense Res. and Dev. 2, 261 (1992).
Agrawal et al., Clin. Pharmacokinet. 28, 7-16 (1995).
Southern, J. Mol. Biol. 98, 503-517 (1975).
Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press (1989).
Agrawal et al., Natl. Acad. Sci. USA 88, 7595-7599 (1991).
Beaucage and Caruthers, Tetrahedron Lett. 22, 1859-1862 (1981).
Graham et al., Nucleic Acics Res. 21, 3737-3743 (1993).
Pfitzner and Moffatt, J. Am. Chem. Soc. 87, 5661-5770 (1965).
Jones and Moffatt, in Methods in Carbohydrate Chemistry, vol. 6, pp. 315-322 (1972).
Albright and Goldman, J. Am. Chem. Soc. 87, 4214 (1965).
Berger et al., Nucleosides and Nucleotides 6, 395-396 (1987).
Dess and Martin, J. Am. Chem. Soc. 113, 7277-7287 (1991).

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