Aldehyde modifiers would be attractive electrophilic substitutions in oligonucleotides since they are able to react with amino groups to form a Schiff’s base, with hydrazino groups to form hydrazones, and with semicarbazides to form semi-carbazones. The Schiff’s base is unstable and must be reduced with sodium borohydride to form a stable linkage but hydrazones and semicarbazides are very stable linkages.
Our collaboration with ELITechGroup, formerly Epoch Biosciences, has allowed us to offer 5'-Aldehyde-Modifier C2 Phosphoramidite. The acetal protecting group is sufficiently hydrophobic for use in RP HPLC and cartridge purification and is readily removed after oligonucleotide synthesis under standard oligonucleotide detritylation conditions with 80% acetic acid / 20% water or 2% aqueous trifluoroacetic acid during cartridge purification.
A formylindole nucleoside analogue has been used to introduce aldehyde groups within an oligonucleotide or at the 5’ terminus. This product has no protecting group on the aldehyde, which means that deprotection of the modified oligonucleotide can be done without changing preferred conditions.