In recent times both basic and applied molecular biology studies have made extensive use of modified oligonucleotides as tools in the study of gene regulation, drug discovery and diagnostics. In particular, aldehyde modified oligonucleotides have been used in applications such as bio-conjugation1 and micro-array2,3 in hybridization-based assays.
The conjugation reaction between aldehyde and hydrazides, hydrazines, semicarbazides or aminooxy fynctionalized synthons is highly chemically selective and efficient.1-3 It was shown that the resulting Schiff-base is relatively stable linker,2 however it can be stabilized further by reduction to the corresponding hydrazine.4 Most methods are orthogonal to the most popular conjugation methods utilizing Michael addition reaction or activated carboxylates. Therefore the aldehyde functional group will not interfere with those reactions and can be used, when other functional groups involved in the parallel process.
Bio-synthesis offers not only wide varieties of 3’-, 5’- and internally aldehyde modified oligonucleotides and also their 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.