Synthesis of aminoglycoside-modified oligonucleotides

Organic Letters

Volumn 2, Issue 12, 2000, Pages 1693-1696

  Tona, Rolf ^a   Bertolini, Reto ^a   Hunziker, Jürg ^a  

^a UNIVERSITY OF BERN   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLYCOSIDE; DNA; OLIGONUCLEOTIDE; RNA;

ARTICLE; BASE PAIRING; CHEMISTRY; CIRCULAR DICHROISM; CONFORMATION; METABOLISM; SYNTHESIS; ULTRASTRUCTURE;

AMINOGLYCOSIDES; BASE PAIRING; CIRCULAR DICHROISM; DNA; NUCLEIC ACID CONFORMATION; OLIGONUCLEOTIDES; RNA;

EID: 0034658925     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol005797d     Document Type: Article

References (21)

1. Kornberg, A.; Baker, T. A. DNA Replication; W. H. Freeman Co.: New York, 1992.
2. http://medlib.med.utah.edu/RNAmods/. Rozenski, J.; Crain, P. F.; McCloskey, J. A. Nucleic Acids Res. 1999, 27, 196.
3. Robertson, K. D.; Jones, P. A. Carcinogenesis 2000, 21, 461.
4. This modification is also referred to as nucleoside J. (a) Gommers-Ampt, J. H.; van Leeuwen, F.; de Beer, A. L. J.; Vliegenthart, J. F. G.; Dizdaroglu, M.; Kowalak, J. A.; Crain, P. F.; Borst, P. Cell 1993, 75, 1129.
5. (b) van Leeuwen, F.; Wijsman, E. R.; Kuyl-Yeheskiely, E.; van der Marel, G. A.; van Boom, J. H.; Borst, P. Nucleic Acids Res. 1996, 24, 2476.
6. Gao, Y.; Robinson, H.; Wijsman, E. R.; van der Marel, G. A.; van Boom, J. H.; Wang, A. H.-J. J. Am. Chem. Soc. 1997, 119, 1496.
7. van Leeuwen, F.; de Kort, M.; van der Marel, G. A.; van Boom, J. H.; Borst, P. Anal. Biochem. 1998, 258, 223.
8. Bertolini, R.; Hunziker, J. Unpublished data.
9. Hunziker, J. Bioorg. Med. Chem. Lett. 1999, 9, 201.
10. de Kort, M.; Ebrahimi, E.; Wijsman, E. R.; van der Marel, G. A.; van Boom, J. H. Eur. J. Org. Chem. 1999, 2337.
11. Cline, R. E.; Fink, R. M.; Fink, K. J. Am. Chem. Soc. 1959, 81, 2521.
12. 13C NMR, and mass spectroscopy.
13. Park, W. K. C.; Auer, M.; Jaksche, H.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 10150.
14. The mixture of these two compounds could only be separated by silica gel chromatography with substantial loss of 18. Nevertheless, the ease of preparation of 18 outweighted the poor yields of this strategy.
15. Conolly, B. A. In Oligonucletides and Analogues; Eckstein, F., Ed.; Oxford University Press: Oxford, 1991; pp 155-183.
16. +-form) 22, calcd 3155.0, found 3154.9; 26, calcd 3363.3, found 3364.4. Matrix conditions as described in the following: Pieles, U.; Zürcher, W.; Schär, M.; Moser, H. E. Nucleic Acids Res. 1993, 21, 3191.
17. The HPLC trace of crude ODNs 22 and 26 showed that a substantial amount of byproducts was present - presumably not fully deprotected ODNs which arise from the capping step of the oligo synthesis. Acetic anhydride could acylate the trifluoroacetamide functions of the diaminoglucose residues and these acetamides might not be fully deprotected under standard deprotection conditions (concentrated ammonia at 55°C for 16 h). MALDI-ToF MS analysis of these byproducts was inconclusive.
18. Saenger, W. Principles of Nucleic Acid Structure; Springer-Verlag: New York. 1984.
19. 5-Aminoalkyl-and alkynyl-modified pyrimidine oligonucleotides also bind stronger to complementary DNA under low salt conditions and neutral pH than their unmodified counterparts, (a) Hashimoto, H.; Nelson, M. G.; Switzer, C. J. Am. Chem. Soc. 1993, 115, 7128.
20. (b) Heystek, L. E.; Zhou, H.; Dande, P.; Gold, B. J. Am. Chem. Soc. 1998, 120, 12165.
21. Tor, Y. Angew. Chem., Intl. Ed. 1999, 38, 1579.