General process for the preparation of cyclic oligonucleotides

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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435 6, 435 911, 536 221, 536 2533, C07H 2104, C12Q 168

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06153742&

ABSTRACT:
The preparation process starts with a protected nucleotide which is anchored through its phosphate group with an anchoring group that links the phosphate group to a polymeric support, its 5'-hydroxyl group is protected for chain elongation and its 3'-terminal phosphate group is protected with a chain phosphate protecting group. Elongation is carried out under conditions in which the protecting groups of adenine, cytosine and guanine remain unaltered and thymine and uracil groups are not protected. Chain phosphate protecting groups are removed from the obtained cyclic anchored intermediate. Then the product is cleaved from the polymeric support and the protecting groups of the nucleobases are removed. The process has the advantages of general utility for any bases and any size of cycle and of providing high yields with minor by-products. The cyclic oligonucleotides obtained have potential use as antisense products and probes, as well as in therapeutics and in diagnosis.

REFERENCES:
Eritja et al. NPE-Resin, A new approach to the solid-phase synthesis of protected peptides and oligonucleotides I: Synthesis of the supports and their application to oligonucleotide synthesis.Tetrahedron Letters, vol. 32, No. 11, pp. 1511-1514, 1991.
M. V. Rao, et al/Nucleic Acids Research vol. 17, #20 1989 p. 8221-8240.
G. Prakash, et al/Struc. Effects in Rec . . . , 1992 Amer. Chem. vol. 114 p. 3523-3527.
Dolinnaya N. et al/Oligonucleotide circ . . . , 1993 vol. 21, #23, pp. 5403-5407.
Conte M.R. et al/Automated Synthesis of . . . , 12(3&4), 351-358 (1993).
De Napoli L., et al/Facile Prep of Cyclic . . . , 1993, J. Chem. Soc. Perkins Trans. vol. I, pp. 747-749.

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