SOLID SUPPORT SYNTHESIS OF 3'-TAILED OLIGONUCLEOTIDES VIA A LINKING MOLECULE

摘要

Oligonucleotides having a low molecular weight tail molecules joined to the 3' terminus of the oligonucleotide via a linking molecule of structure (I) or (II) wherein Z is (III), (IV), (V), (VI) or (VII), m and m' are positive integers less than 11, n is 0 or 1 and Q is a connecting group, are synthesized by selectively reacting three independent functional groups on the linking molecule, i.e., an amine, a primary hydroxyl and a secondary hydroxyl, in a stepwise manner. A tail molecule R is first connected to the amino functionality of the linking molecule. Next the linking molecule-tail molecule combination is attached to a solid state support via the secondary hydroxyl group. The oligonucleotide is systematically stepwise synthesized beginning on the primary hydroxyl group followed by release of the oligonucleotide having the low molecular weight tailed joined to its 3' terminus from the solide state support.