Xylo-LNA analogues

Details Xylo-LNA analogues Xylo-LNA analogues

2006-08-01

2006-08-01

Epps Ford, Janet (Department: 1633)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

C536S022100, C536S023100, C536S024300, C536S024500

Reexamination Certificate

active

07084125

ABSTRACT:
Based on the above and on the remarkable properties of the 2′-O,4′-C-methylene bridged LNA monomers it was decided to synthesise oligonucleotides comprising one or more 2′-O,4′-C-methylene-β-D-xylofuranosyl nucleotide monomer(s) as the first stereoisomer of LNA modified oligonucleotides. Modelling clearly indicated the xylo-LNA monomers to be locked in an N-type furanose conformation. Whereas the parent 2′-deoxy-β-D-xylofuranosyl nucleosides were shown to adopt mainly an N-type furanose conformation, the furanose ring of the 2′-deoxy-β-D-xylofuranosyl monomers present in xylo-DNA were shown by conformational analysis and computer modelling to prefer an S-type conformation thereby minimising steric repulsion between the nucleobase and the 3′-O-phopshate group (Seela, F.; Wömer, Rosemeyer, H.Helv. Chem. Acta1994, 77, 883). As no report on the hybridisation properties and binding mode of xylo-configurated oligonucleotides in an RNA context was believed to exist, it was the aim to synthesise 2′-O,4′-C-methylene-β-D-xylofuranosyl nucleotide monomer and to study the thermal stability of oligonucleotides comprising this monomer. The results showed that fully modified or almost fully modified Xylo-LNA is useful for high-affinity targeting of complementary nucleic acids. When taking into consideration the inverted stereochemistry at C-3′ this is a surprising fact. It is likely that Xylo-LNA monomers, in a sequence context of Xylo-DNA monomers, should have an affinity-increasing effect.

REFERENCES:
patent: 6013639 (2000-01-01), Peyman et al.
patent: 6268490 (2001-07-01), Imanishi et al.
patent: 6316612 (2001-11-01), Matulic-Adamic et al.
patent: 6525191 (2003-02-01), Ramasamy
patent: 2002/0068708 (2002-06-01), Wengel et al.
patent: 2003/0018186 (2003-01-01), Ramasamy et al.
patent: 0538194 (1999-04-01), None
patent: WO98/22489 (1998-05-01), None
patent: WO98/39352 (1998-09-01), None
patent: WO 99/60855 (1999-02-01), None
patent: WO99/14226 (1999-03-01), None
Norrild et al. A highly stereoselective synthesis of 1-amino-2,5-anhydro-1-deoxyhexitois via 2-trifluoromethyl-oxazolinium intermediates. Carbohydrate Research, vol. 297, pp. 261-272, 1997.
Stanley Crooke, Antisense Research and Applications, Chapter 1, Basic Principles of Antisense Therapeutics, Jul. 1998, Springer-Verlag Press, Berlin, Heidelberg, New York, pp. 1-50.
Tarkoy et al.,Helv. Chim. Acta, 76:481 (1993), pp. 481-510.
Tarkoy et al.,Angew. Chem., Int. Ed. Engl., 32:1432 (1993), vol. 32, No. 10 pp. 1432-1434.
Egli et al.,J. Am. Chem. Soc., 115:5855 (1993), pp. 5855-5856.
Tarkoy et al.,Helv. Chim. Acta, 77:716 (1994), pp. 716-744.
Bolli et al.,Angew. Chem., Int. Ed. Engl., 34:694 (1995), vol. 34, No. 6, pp. 694-696.
Bolli et al.,Helv. Chim. Acta, 78:2077 (1995), pp. 2077-2096.
Litten et al.,Bioorg. Med. Chem. Lett., 5:1231 (1995), pp. 1231-1234.
Litten et al.,Helv. Chim. Acta, 79:1129 (1996), pp. 1129-1146.
Bolli et al.,Chem. Biol., 3:197 (1996), pp. 197-205.
Bolli et al.,Nucleic Acids. Res., 24:4660 (1996), pp. 4660-4667.
K.H. Altmann et al.,Tetrahedron Lett., 35::2331 (1994), pp. 2331-2334.
K. H. Altmann et al.,Tetrahedron Lett., 35:7625 (1994), pp. 7625-7628.
Marquez et al.,J. Med. Chem., 39:3739 (1996), pp. 3739-3747.
Ezzitouni et al.,J. Chem. Soc., Perkin Trans., 1:1073 (1997), pp. 1073-1078.
Jones et al.,J. Am. Chem. Soc., 115:9816 (1993), pp. 9816-9817.
Wang et al.,Bioorg. Med. Chem. Lett., 7: 229 (1997), pp. 229-232.
Yannopoulus et al.,Synlett, 378 (1997), pp. 378-380.
Chima, 36thIUPAC Congress, organized by the Swiss Chemical Society. Poster No. SB-B4: Steffens, R. and Leumann Ch. Tricyclo-DNA: synthesis, enzymatic stability, and pairing properties.
Nielsen, Master Thesis (Odense University, Denmark), p. 67-71 (1995).
Youssefyeh et al.,J. Org. Chem., 44:1301 (1979), pp. 1301-1308.
Jones et al.,J. Org. Chem., 44:1309 (1979), pp. 1309-1317.
Yang et al.,Tetrahedron Lett., 33:37 (1992), pp. 37-40.
Thrane et al.,Tetrahedron, 51:10389 (1995), pp. 10389-10402.
Nielsen et al.,Bioorg. Med. Chem., 3:1493 (1995), pp. 1493-1502.
Freier et al.,Nucleic Acid Research, 25:4429-4443 (1997).
Haly et al.,SYNLETT, 687-689 (1996).
Zou et al.,Tetrahedron Lett., 37:941-944 (1996).
Herdewijn.,Liebigs Ann., 1337-1348 (1996).
Obika et al.,Tetrahedron Lett., 39:5401-5404 (1998).
Obika et al.,Tetrahedron Lett., 38:8735-8738 (1997).
7thAntisense Symposium, Nov. 21-22, 1997. Poster No. 32 and 33: Obika, D.N.; Morio, K. and Imanishi, T. Synthesis and properties of oligonucleotides containing novel bicyclic nucleosides with a fixed N-form sugar puckering.
Chima, 36thIUPAC Congress, organized by the Swiss Chemical Society. Poster No. SB-B12: Egtger, A. and Leumann Ch. Designe, synthesis and properties of bicyclo [3.2.1]-amio nucleic acids.
Chima, 36thIUPAC Congress, organized by the Swiss Chemical Society. Poster No. SB-B5: Epple, C. Ch., Pompizi, I. and Leumann Ch. Bicyclo [3.2.1]-DNA: an oligonucleotide analogue with a conformationally preorganized Phosphodiester backbone and a flexible sugar-base linkage.
Sep. 6-10, 1998: 13thInternational Round Table—Nucleoside, Nucleotides and their Biological Applications, Montpeilleir: Oral Communication 1: Wang, G. and Gunic, E. “Conformationally Locked Nucleoside Analogs. Synthesis of 2′-Deoxy-2′-C, 4′-C-Bridged Bicyclic Nucleoside”.
Sep. 6-10, 1998: 13thInternational Round Table—Nucleoside, Nucleotides and their Biological Applications, Montpeilleir: Poster No. 288: Meldgaard, M. et al., “LNA (Locked Nucleic Acids): Synthesis and Thermal Denaturation Studies”.
Sep. 6-10, 1998: 13thInternational Round Table—Nucleoside, Nucleotides and their Biological Applications, Montpeilleir: Poster No. 287 and Proceeding: Koshkin, A. A. et al., “Locked Nucleic Acids as synthetic RNA Mimics for Effective Complementary Recognition.”
Sep. 6-10, 1998: 13thInternational Round Table—Nucleoside, Nucleotides and their Biological Applications, Montpeilleir: Poster No. 67: Nielsen, P. and Wengel, J. “A New Convergent Synthetic Approach Towards a-and β-LNA (Locked Nucleic Acids)”.
Oct. 8, 1998: Antisense 98, Targeting the Molecularl Basis of Disease: Poster No. 24: Havsteen, M. et al., “LNA (Locked Nucleic Acids): A new Class of High Affinity Nucleic Acids With Prime Potential as Antisense and Antigene Agents”.
Jan. 21, 1998: National Seminar on Perspectives in Interfacial Areas of Chemistry and Biology, Delhi University: Wengel, J. “LNA (Locked Nucleic Acids): Synthesis and High Affinity Nucleic Acid Recognition—Stop the Twisting.”
27 Marts 1998: Workshop of Young European Bioorganic Chemists, Munchen: Wengel, J. “LNA (Locked Nucleic Acids): Synthesis and High Affinity Nucleic Acid Recognition—Stop the Twisting.”
Aug. 20, 1998: Årsmødet for Center for Medicinsk Biotecknologi, KVL: Wengel, J. “LNA (Locked Nucleic Acids)”ations, Montpeilleir: Oral Communication 1: Wang, G. and Gunic, E. “Conformationally Locked Nucleoside Analogs. Synthesis of 2′-Deoxy-2′-C, 4′-C-Bridged Bicyclic Nucleoside”.
Sep. 7, 1998: 13thInternational Round Table—Nucleoside, Nucleotides and their Biological Applications, Montpeilleir: Oral Communication 2: Wengel, J “LNA (locked Nucleic Acids)”.
Sep. 8, 1998: Meeting in Lund, Sweden: Jakobsen, M. H. “LNA (Locked Nucleic Acids): A new Class of High Affinity Nucleic Acids With Prime Potential as Antisense and Antigene Agents”.
Nielsen et al.,J. Chem. Soc., Perkin Trans., 1:3423-3433 (1997).
Nielsen et al.,Chem. Commun., 9:825-826 (1997).
Singh et al.,Chem. Commun., 455-456 (1998).
Koshkin et al.,Tetrahedron, 54:36073630 (1998).
Koshkin et al.,Tetrahedron Lett., 39:4381-8384 (1998).
Singh et al.,Chem. Commun., 1237-1248 (1998).
Singh et al.,J. Org. Chem., 63:6078-6079 (1998).
Christensen et al.,J. Am. Chem. Soc., 120:5458-5463 (1998).
Koshkin et al.,J. Org

Affiliated with

Also associated with

Rating

Xylo-LNA analogues does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Xylo-LNA analogues, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Xylo-LNA analogues will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3692458