H-Phosphonate modification has a setup charge of $250.00 per order for special synthesis reagents .
H-phosphonoamidites are deoxynucleoside amidites modified such that, when incorporated into an oligonucleotide, that base position will have an H-phosphonate backbone linkage instead of the standard phosphodiester linkage. In the H-phosphonate linkage, one of the oxygen bound to the phosphorus atom in a phosphodiester linkage has been replaced by hydrogen. H-phosphonate-modified oligos are typically synthesized when a researcher wants to prepare a S-35 radiolabeled phosphorothioate linkage (1). For the radiolabeled phosphorothioate, an H-phosphonate linkage is incorporated at the desired position using phosphoramidite chemistry, and then S-35 is used to replace the hydrogen atom via a sulfurization reaction (2). For the phosphoroamidate, N,N-dimethylaminoethylamine is reacted with the H-phosphonate to form the substituted linkage. Phosphoroamidates, being a cationic linkage, may provide nuclease resistance and improved cell permeability (3).
1. Maier, M.A., Guzaev, A.P., Manoharan, M. Synthesis of Chimeric Oligonucleotides Containing Phosphodiester, Phosphorothioate, and Phosphoramidate Linkages. Org. Lett. (2000), 2: 1819-1822.
2. Wallin, R., Kalek, M., Bartoszewicz, A., Thelin, M., Stawinski, J. On the Sulfurization of H-Phosphonate Diesters and Phosphite Triesters Using Elemental Sulfur.Phosphorus, Sulfur, and Silicon (2009), 184: 908-916.
3. Letsinger, R.L., Singman, C.N., Histand, G., Salunkhe, M. Cationic Oligonucleotides.J. Am. Chem. Soc. (1988), 1110: 4470-4471.