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

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2144-7. doi: 10.1016/j.bmcl.2009.02.121. Epub 2009 Mar 4.

Abstract

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 modification efficacy, we used the amino-linker (aminoethoxycarbonyl)aminohexyl group (ssH-linker), for solid-support conjugation. In the ssH-linker terminal modification, 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 modification for the solid-support conjugation of functional molecules.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Chemistry, Pharmaceutical / methods*
  • Glycine / analogs & derivatives
  • Oligonucleotides / chemical synthesis*
  • Oligonucleotides / genetics

Substances

  • Oligonucleotides
  • aminoethoxyvinylglycine
  • Glycine