Introduction of a universal solid support for oligonucleotide synthesis

Nucleosides and Nucleotides

Volumn 16, Issue 1-2, 1997, Pages 67-80

  Scheuer Larsen, Claus ^a   Rosenbohm, Christoph ^a   Jørgensen, Thomas J D ^a   Wengel, Jesper ^a,b  

^a UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

OLIGONUCLEOTIDE;

ACETYLATION; ARTICLE; DERIVATIZATION; DRUG SYNTHESIS; GENETIC LINKAGE; MOLECULAR BIOLOGY; NONHUMAN; NUCLEOTIDE METABOLISM; SIALYLATION;

EID: 0031056452     PISSN: 07328311     EISSN: None     Source Type: Journal    
DOI: 10.1080/07328319708002522     Document Type: Article

References (22)

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8. For a recent example, see: Koga, M.; Wilk, A.; Moore, M. F.; Scremin, C. L.; Zhou, L.; Beaucage, S. L. J. Org. Chem. 1995, 60, 1520.
9. Recently, photochemical cleavage of protected or unprotected oligonucleotides from o-nitrobenzyl linked solid supports, allowing subsequent 3′-end conjugation, was reported: (a) Greenberg, M. M.; Gilmore, J. L. J. Org. Chem. 1994, 59, 746. (b) Yoo, D. J., Greenberg, M. M. J. Org. Chem. 1995, 60, 3358. (c) Venkatesan, H., Greenberg, M. M. J. Org. Chem. 1996, 61, 525.
10. Recently, photochemical cleavage of protected or unprotected oligonucleotides from o-nitrobenzyl linked solid supports, allowing subsequent 3′-end conjugation, was reported: (a) Greenberg, M. M.; Gilmore, J. L. J. Org. Chem. 1994, 59, 746. (b) Yoo, D. J., Greenberg, M. M. J. Org. Chem. 1995, 60, 3358. (c) Venkatesan, H., Greenberg, M. M. J. Org. Chem. 1996, 61, 525.
11. Recently, photochemical cleavage of protected or unprotected oligonucleotides from o-nitrobenzyl linked solid supports, allowing subsequent 3′-end conjugation, was reported: (a) Greenberg, M. M.; Gilmore, J. L. J. Org. Chem. 1994, 59, 746. (b) Yoo, D. J., Greenberg, M. M. J. Org. Chem. 1995, 60, 3358. (c) Venkatesan, H., Greenberg, M. M. J. Org. Chem. 1996, 61, 525.
12. The idea of applying phosphorus chemistry for linking functionalised monomers in a combinatorial fashion has been exploited, see e.g.: Hébert, N.; Davis, P. W.; Debaets, E. L.; Acevedo, O. L. Tetrahedron Lett. 1994, 35, 9509.
13. Hardy, P. M.; Holland, D.; Scott, S.; Garman, A. J.; Newton, C. R.; McLean, M. J. Nucleic Acids Res. 1994, 22, 2998. Two 3,4-dihydroxytetrahydrofuran rings linked together as a succinate diester, derivatised at the two remaining hydroxyl groups as a 4,4′-dimethoxytrityl ether and as a standard phosphoramidite, was used as adapter (TOPS™) for synthesis of two different oligonucleotides in one synthesis. Cleavage of the 3′-OH free oligonucleotides, via cyclic phosphate formation, required prolonged treatment with concentrated ammonia (overnight, 80°C) or treatment with 40% methylamine (8 h, 60°C). This strategy is also useful for synthesis of 3′-end modified oligonucleotides if TOPS™ is incorporated as the first building block on a standard support.
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15. (b) deBear, J. S.; Hayes, J. A.; Koleck, M. P.; Gough, G. R. Nucleosides Nucleotides 1987, 6, 821. Release of oligodeoxynucleotides from a LCAA-CPG support containing a 2′-O-benzoylated uridine linker was accomplished by treatment with concentrated ammonia (16-24 h, 60-65°C).
16. (c) Schwartz, M. E.; Breaker, R. R.; Asteriadis, G. T.; Gough, G. R. Tetrahedron Lett. 1995, 36, 27. A nucleotide adapter (2′(3′)O-(4,4′-dimethoxytrityl)-3′(2′)-O-benzoyl- 5′-O-(2- cyanoethoxy(diisopropyl)phosphino)uridine) was used, after coupling to a polystyrene thymidine type support and detritylation, for subsequent synthesis of DNA and RNA. After complete synthesis, concentrated ammonia (48 h, 65°C) was used for deprotection and cleavage of the 3′-OH free oligodeoxynucleotides from the support and adapter.
17. 7,8 can be explained by the difficulty of cleaving a phosphate diester resulting from release of the cyanoethyl phosphate protecting group during ammonia treatment. Tentatively we believe that the use of chloroacetyl (in compound 6) as protecting group for the hydroxyl group subsequently to be responsible for the nucleophilic attack leading to the desired 3′-OH free oligonucleotide, allows milder and faster cleavage of a phosphate triester intermediate. In model experiments we have shown that the 3-O- chloroacetyl group is removed almost instantaneously by concentrated ammonia.
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