The (fluorenylmethyl)carbamoyl (Fmoc) group has been shown to be a useful amine protecting group for amine modification of oligonucleotides.⁽¹⁾ It is removed during cleavage/deprotection with ammonium hydroxide. Alternatively, the Fmoc group can be removed before cleavage of the oligonucleotide from the solid support,⁽²⁾ e.g., with piperidine, simplifying the acylation process. After the acylation is complete, the labeled oligonucleotide can then be cleaved from the support and further deprotected with ammonium hydroxide.
For applications requiring a nucleobase-tethered amine at internal or 5' positions, we offer this Fmoc-protected compound Fmoc-Amino-Modifier-C6-dT CE-Phosphoramidite (BA0287), which offers the possibility of on-bead acylation as discussed above. It is an alternative to the venerable Amino-Modifier-C6-dT CE-Phosphoramidite (BA0015 / LK2135) which bears a trifluoroacetyl (TFA) protecting group. The TFA group cannot be removed without cleavage of the oligonucleotide from the resin.

For 3'-amino-modification involving Fmoc-deprotection, see BA0299 and BA0307, and LK2350.

Ref:

1. Nelson, P. S.; Kent, M.; Muthini, S. Nucl. Acids Res. 1992, 20, 6253-6259.
2. For example, see: (a) Gartner, Z. J.; Kanan, M. W.; Liu, D. R. J. Am. Chem. Soc. 2002, 124, 10304-10306; see Supporting Information, p. 3. (b) Gartner, Z. J.; Tse, B. N.; Grubina, R.; Doyon, J. B.; Snyder, T. M.; Liu, D. R. Science 2004, 305, 1601-1605; see Supporting Online Material, p. 2.