Bioreversible oligonucleotide conjugates by site-specific derivatization

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 7, 1997, Pages 871-876

  Iyer, Radhakrishnan P ^a   Ho, Nan Hui ^a   Yu, Dong ^a   Agrawal, Sudhir ^a  

^a HYBRIDON INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; OLIGONUCLEOTIDE;

ARTICLE; CONJUGATION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROLYSIS; IN VITRO STUDY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STEREOCHEMISTRY;

EID: 0030907794     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00119-4     Document Type: Article

References (26)

1. For a recent review see: Fidanza, J. A.; Ozaki, H.; McLaughlin, L. W. In Protocols for Oligonucleotide Conjugates, Agrawal, S. Ed., Humana Press, New Jersey, 1994, pp. 121-143; For applications of phosphoramidite chemistry in the preparation of oligonucleotide conjugates, see: Beaucage, S. L.; Iyer, R. P. Tetrahedron, 1993, 49, 1925.
2. For a recent review see: Fidanza, J. A.; Ozaki, H.; McLaughlin, L. W. In Protocols for Oligonucleotide Conjugates, Agrawal, S. Ed., Humana Press, New Jersey, 1994, pp. 121-143; For applications of phosphoramidite chemistry in the preparation of oligonucleotide conjugates, see: Beaucage, S. L.; Iyer, R. P. Tetrahedron, 1993, 49, 1925.
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12. (d) For a recent study of fast deprotection using PNT nucleosides, see: Iyer, R. P.; Yu, D., Habus, I., Ho, N. -H., Johnson, S., Devlin, T.; Jiang, Z.; Zhou, W.; Xie, J.; Agrawal, S. Tetrahedron, 1997, (in press).
13. For examples, see: (a) Kuijpers, W. H. A.; Huskens, J.; Koole, L. H.; van Boeckel, C. A. A. Nucl. Acids Res. 1990, 18, 5197,
14. (b) Also see references 4a-d.
15. 2ppm.
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17. (b) For a review, see: Beaucage, S. L.; Iyer, R. P. Tetrahedron, 1993, 49, 1925;
18. 7d was not successful;
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21. p isomers, were treated with chymotrypsin to generate the parent trinucleoside. The trinucleoside was then digested sequentially with snake venom phosphodiesterase, and alkaline phosphatase to give the corresponding dinucleoside phosphorothioates which was analyzed by reversed-phase HPLC. Absolute configurations were assigned by comparison of retention times with authentic samples of known configuration (see reference 3a).
22. (a) Toone, E. J.; Werth, M. J.; Jones, J. B. J. Am. Chem. Soc. 1990, 112, 4946, and references therein;
23. (b) For a recent application of this model, see: Bugg, T. D. H.; Lewin, A. M.; Catlin, E. R. J. Chem. Ed. 1997, 74, 105;
24. (c) Interestingly, simple 2,6-dimethylbenzoyl esters of terbutaline® did not biorevert to terbutaline; see: Svensson, L. -Å.; Tunek, A. Drug. Metab. Rev. 1988, 19, 165.
25. Iyer, R. P.; Yu, D.; Ho, N.-H.; Devlin, T.; Agrawal, S. J. Org. Chem. 1995, 60, 8132
26. Alternatively, the use of oxalyl-linked CPG expedited the cleavage of the oligo from the support; See: Alul, R. H.; Singman, C. N.; Zhang, G.; Letsinger, R. L. Nucl. Acids Res. 1991, 19, 1527.