Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates

Details Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates

1996-12-20

1999-01-12

Kunz, Gary L.

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

Organic compounds

Carbohydrates or derivatives

536 2612, 536 2614, C07H 1910, C07H 1920

Patent

active

058592334

ABSTRACT:
The invention provides a method of synthesizing oligonucleotide N3'.fwdarw.P5' phosphoramidates using an amine-exchange reaction of phosphoramidites in which a -deprotected 3'-amino group of a solid phase supported oligonucleotide chain is exhanged for the amino portion of a 5'-phosphoramidite of an incoming monomer which has a protected 3'-amino group. The resulting internucleotide phosphoramidite linkage is then oxidized to form a stable protected phosphoramidate linkage. The method of the invention greatly improves product yields and reduces reagent usage over currently available methods for synthesizing the above class of compound.

REFERENCES:
patent: 5476925 (1995-12-01), Letsinger et al.
Abraham, et al., "A Phosphoramidite-Based Synthesis of Phosphoramidate Amino Acid Diesters of Antiviral Nucleosides," Nucleosides & Nucleotides 13: 1891-1903 (1994).
Agrawal, et al., "Oligodexoynucleoside Phosphoramidates and Phosphorothioates as Inhibitors of Human Immunodeficiency Virus," Proc. Natl. Acad. Sci. USA 85: 7079-7083 (1988).
Azhayev, et al., "Synthesis of Phosphoramidate Analogs of Ribonucleoside Phosphates," Coll. Czechoslov. Chem. Commun. 44: 792-798 (1979).
Azhayev, et al., "Aminonucleosides and Their Derivatives. IX. Synthesis of Short Oligoribonucleotide with Phosphoramide Internucleotide attached!.
Azhayev, et al., "Synthesis of Phosphoramidate Analogues of Short Oligoribunucleotides," Nuc. Acids Res., Symp. Series 9:251-254 (1981).
Bannwarth, "166. Solid-Phase Synthesis of Oligodeoxynucleotides Containing Phosphoramidate Internucleotide Linkages and Their Specific Chemical Cleavage," Helvetica Chim. Acta 71: 1517-1527 (1989).
Chen, et al., "Synthesis of Oligonucleotides N3'.fwdarw.P5' Phosphoramidates," Nuc. Acids Res. 23:2661-2668 (1995).
Gryaznov and Letsinger, "Synthesis and Properties of Oligonucleotides Containing Aminodeoxythymidine Units," Nuc. Acids Res. 20:3403-3409 (1992).
Gryaznov and Chen, "Oligonucleotide N3'.fwdarw.N5' Phosphoramidates: Synthesis and Hybridization Properties," J. Am. Chem. soc. 116:3143-3144 (1994).
Gryaznov, et al., "Oligonucleotide N3'.fwdarw.N5' Phosphoramidates," Proc. Natl. Acad. Sci. USA 92:5798-5802 (1995).
Herdewijn, et al., "Synthesis and Biological Activity of the Mono- and Diamino Analogues of 2'-Deoxyadenosine, Cordycepin, 9-(3-deoxy-.beta.-D-threopentofuranosyl)-adenine," Nucleosides & Nucleotides 8: 1231-1257 (1989).
Krayevsky, et al., "Synthesis of Oligonucleotides with 5'.fwdarw.3' Phosphoamidoester Bond," Nuc. Acids Res., Symp. Series No. 9, pp. 203-205 (1981).
Mag and Engels, "Synthesis and Selective Cleavage of Oligodeoxyribonucleosides Containing Non-Chiral Internucleotide Phosphoramidate Linkages," Nuc. Acids Res. 17:5973-5988 (1989).
Mag, et al., "Synthesis and Selective Cleavage of an Oligodeoxynucleotide Containing a Bridged Non-Chiral Internucleotide 3'-Phosphoramidate Linkage," Tetrahedron Lett. 33:7319-7322 (1992).
Mag and Engels, "Synthesis of Dinucleotides Containing a Bridged Non-Chiral Internucleoside 5'-or 3'-phosphoramidate Linkage," Tetrahedron 50:10225-10234 (1994).
Robles, J., et al., "Stepwise Solid-Phase Synthesis of Nucleopeptide Phac-Ser(p.sup.5' CATCAT) -Gly-Asp-OH from Adenovirus-2 Nucleoprotein," Tetrahedron Lett. 35:4449-4452 (1994).
Saha, et al., "Synthesis of Modified Achiral Internucleoside Linkages: -NCHCH2CH2-Linked Oligonucleosides," Tetrahedron Lett. 34:6017-6020 (1993).
Zaitseva, et al., "Aminonucleosides and Their Derivatives. X. 2'-deoxydinucleoside Phosphates and Deoxydinucleotides with Phosphoamidate attached!.
Zielinski and Orgel, "Oligomerization of Activated Derivatives of 3'-amino-3'-deoxyguanosine on poly (C) and poly (G) Templates," Nuc. Acids Res. 13:2469-2484 (1985).
Zielinski and Orgel, "Autocatalytic Synthesis of a Tetranucleotide Analog," Nature 327:346-347 (1987).
Zielinski and Orgel, "Oligoaminonucleotide Phosphoramidates, Oligomerization of Dimers of 3'-amino-3'-deoxy-nucleotides (GC and CG) in Aqueous Solution," Nuc. Acids Res. 1699:1715 (1987).

Affiliated with

Also associated with

Rating

Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1517842