Procedure for the solid phase synthesis of .sup.35 S-labeled oli

Details Procedure for the solid phase synthesis of .sup.35 S-labeled oli Procedure for the solid phase synthesis of .sup.35 S-labeled oli

1994-11-07

1998-11-10

Kight, John

Drug, bio-affecting and body treating compositions

Radionuclide or intended radionuclide containing; adjuvant...

In an organic compound

549 1, 424 165, A61K 5100, A61M 3614

Patent

active

058339442

ABSTRACT:
This invention provides a novel compound for .sup.35 S-labelling oligonucleotides. The compound is .sup.35 S-3H-1,2-benzodithiol-3-one-1,1 dioxide (1) ##STR1## wherein the asterisk indicates the position of the .sup.35 S. Also provided is a method of synthesizing this compound, comprising first contacting .sup.35 S-thiobenzoic acid (4) with thiosalicylic acid (5) in acid medium to yield the condensation product, .sup.35 S-3 H 1,2-benzodithiol-3-one (2). .sup.35 S-3 H 1,2-benzodithiol-3-one (2) is then oxidized with a suitable oxidating agent such as trifuoroacetic acid and hydrogen perioxide to yield the desired product, .sup.35 S-3H-1,2-benzodithiol-3-one-1,1 dioxide (1). Any oligonucleotide susceptible to oxidative sulfurized by 3H-1,2-benzodithiol-3-one-1,1 dioxide can be labeled by .sup.35 S-3H-1,2-benzodithiol-3-one-1,1 dioxide (1). Accordingly, this invention also provides novel methods for .sup.35 S-labelling oligonucleotides. The compound and methods are useful for tracing biodistribution and degradation of antisense oligonucleotides in pharmacokinetic studies.

REFERENCES:
patent: 4139362 (1979-02-01), Rasheed et al.
patent: 4175186 (1979-11-01), Rasheed et al.
patent: 5003097 (1991-03-01), Beaucage et al.
patent: 5149798 (1992-09-01), Agrawal et al.
Rao and MacFarlane. Tetrahedron Letters, vol. 35, No. 36, pp. 6741-6744 (1994) "Solid Phase Synthesis of Phosphorothiolate Oligonucleotides Using Benzytriethylammonium Tetrathiomolybdate as a Rapid Sulfur Transfer Reagent".
Wyrzykiewicz and Ravikumar. Bioorganic & Medicinal Chemistry Letters, vol. 4, No. 12, pp. 1519-1522 (1994), Efficiency of Sulfurization in the Synthesis of Oligodeoxyribonucleotide phosphorothioates utilizing various sulfurizing reagents.
Hortmann et al. J. Org. Chem., vol. 43, No. 17, pp. 3374-3378 (1978) "3H-1,2-Benzodithiole Oxides: Studies Directed toward the Generation of
Stawinski and Thelin. J. Org. Chem., vol. 56, pp. 5169-5175 (1991) "Nucleoside H-Phosphonates. 13. Studies on 3H-1,2-benzodithiol-3-one Derivatives as Sulfuring reagents for H-Phosphonates and H-Phosphonothioate Diesters".
Iyer et al. J Org. Chem. (1990), 55, pp. 4693-4699, The Automated Synthesis of Sulfur Containing Oligodeoxyribonucleotides using 3H-1,2-benzodithiol-3-One 1,1-Dioxide as a sulfur transfer reagent.
Regan et al. Org. Prep. Proced. Int (1992), 24(4) pp. 488-492 Large-Scale Preparation of the Sulfur transfer reagent 3-H-1,2-benzodithiol-3-one 1,1,-dioxide.
Holum Elements of General, Organic, and Biological Chemistry, 9th edition, pp. 40-42.
The Merck Index, 9.sub.th edition, p. 1162, Compound 8764.
Becaucage and Iyer. Tetrahedron, vol. 49, No. 10, pp. 1925-1963 (1993). "The Functionalization of Oligonucleotides Vici Phosphoramidite Derivatives".
Stawinski et al. Nucleosides and Nucleotides, vol. 10, No. 1-3, pp. 517-518 (1991). "Studies on Sulfurization of Nucleoside H-Phosphonate and H-Phosphonothioate Esters Using 3H-1,2-Benzodithiol-3-One 1,1-dioxide".
Iyer et al. J. Am. Chem. Soc., vol. 112, pp. 1253-1254, "3H-1,2-benzodithiole-3-one 1,1-Dioxide as an Improved Sulfurzing Reagent in the Solid-Phase Synthesis of Oligodeoxyribonucleoside Phosphorothioates".
Iyer et al. Tetrahedron Letters, vol. 35, No. 51, pp. 9521-9524 (1994), Application in the Preparation of site Specifically 35S-labeled Oligonucleotides.
Graham et al. Nucleic Acid Research, vol. 21, No. 16 pp. 3737-3743. "Tritium labeling of antisense oligonucleotides by exchange with tritiated water".
Stein et al., Analytical Biochemistry 188, 11-16 (1990).
Zamecnik and Stephenson, Proc. Natl. Acad. Sci. USA 75, 280-284 (1978).
Agrawal et al., Trends in Biotech. 10, 152-158 (1992).
Uhlmann and Peyman, Chem. Rev. 90, 543 (1990).
See generally, Methods in Molecular Biology, vol. 20: Protocols for Oligonucleotides and Analogs, pp. 165-189 (S. Agrawal, Ed., Humana Press, 1993).
See generally, Oligonucleotides and Analogues: A Practical Approach, pp. 87-108 (F. Eckstein, Ed., 1991).
Khorana et al., J. Molec. Biol. 72, 209 (1972).
Reese, Tetrahedron Lett. 34, 3143-3179 (1978).
Beaucage and Caruthers, Tetrahedron Lett. 22, 1859-1862 (1981).
Beaucage and Iyer, Tetrahedron Lett. 48, 2223 (1992).
Agrawal and Goodchild, Tetrahedron Lett. 28, 3539-3542 (1987).
Connolly et al., Biochemistry 23, 3443 (1984).
Jager et al., Biochemistry 27, 7237 (1988).
Agrawal et al., Proc. Natl. Acad. Sci. USA 85, 7079-7083 (1988).
Padmapriya et al., Antisense Res. & Dev. 4, 185-199 (1994).
Andrad et al., Bioorg. & Med. Chem. Lett., pp. 2017-2022 (1994).
Agrawal et al., Proc. Natl. Acad. Sci. U.S.A. 88, 7595-7599 (1991).
Kawamura et al., Chem. Lett. 1231-1234 (1975).
McKibben and McClelland, J. Chem. Soc., 170-173 (1923).
M. Hudlicky, Oxidation in Organic Chemistry, ACS Monograph 186, 1990.

Affiliated with

Also associated with

Rating

Procedure for the solid phase synthesis of .sup.35 S-labeled oli does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Procedure for the solid phase synthesis of .sup.35 S-labeled oli, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Procedure for the solid phase synthesis of .sup.35 S-labeled oli will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1513703