Aldehyde modified oligonucleotides, their broad utility in bio-conjugation applications and surface attachment methods.
In recent decades both basic and applied molecular biology studies have made extensive use of modified oligonucleotides. Modified oligonucleotides are used as tools in the study of gene regulation, drug discovery and as diagnostics. In particular, aldehyde modified oligonucleotides have been used in applications such as bio-conjugation1, micro-arrays2,3, and in hybridization-based assays.
The conjugation reaction between aldehyde and hydrazides, hydrazines, semicarbazides or aminooxy functionalized synthons is highly chemically selective and efficient.1-3 It was shown that the resulting Schiff-base is a relatively stable linker,2 however it can be stabilized further by reduction to the corresponding hydrazine.4 Most methods used are orthogonal to popular conjugation methods utilizing Michael addition reaction or activated carboxylates. Therefore the aldehyde functional group will not interfere with these reactions and can be used, when other functional groups are used in parallel processes.
Bio-synthesis offers not only a wide variety of 3’-, 5’- and internally aldehyde modified oligonucleotides but also conjugates with peptides, proteins and antibodies.1
References
1. http://www.biosyn.com/Bioconjugation.aspx
2. M. A. Podyminogin, E. A. Lukhtanov and M. W. Reed Nucleic Acid Res., 2001, 29, 5090-5098.
3. S. Raddatz, J. Mueller-Ibeler, J. Kluge, L. Wäß, G. Burdinski, J. R. Havens, T. J. Onofrey, D. Wang, and M Schweitzer Nucleic Acid Res., 2002, 30, 4793-4802.
4. E. N. Timofeev, A. D. Mirzabekov, S. V. Kochetkova and V. L. Florentiev Nucleic Acid Res., 1996, 24, 3142-3148.