Efficient synthesis of oligonucleotide conjugates on solid-support using an (aminoethoxycarbonyl)aminohexyl group for 5′-terminal modification

Solid-support conjugation at the 5 '-terminal primary amine of oligonucleotides is a convenient and powerful method for introducing various functional groups. However, conventional aliphatic amines do not necessarily provide conjugates with sufficient yields. To improve the modi. cation efficacy, we used the amino-linker (aminoethoxycarbonyl) aminohexyl group (ssH-linker), for solid-support conjugation. In the ssH-linker terminal modi. cation, reactive free amino group could be easily presented onto a solid-support due to rapid removal of the amino-protecting group, and activated amino acids or cholesterol molecules could be covalently connected more efficiently than to typical 6-aminohexyl-linkers. Based on these results, the ssH-linker can be a useful terminal modi. cation for the solid-support conjugation of functional molecules. (C) 2009 Elsevier Ltd. All rights reserved.