Method for the chemical synthesis of oligonucleotides

Abstract

The present invention features novel compositions, linkers, derivatized solid supports, and methods for the efficient solid phase synthesis of oligonucleotides, including RNA, DNA, RNA-DNA chimeras, and analogs thereof.

1 . A method for oligonucleotide synthesis comprising:
 a) 5′-Deblocking;   b) Coupling;   c) Oxidation; and   d) Capping;   wherein (a), (b), (c) and (d) are repeated under conditions suitable for the synthesis of the oligonucleotide, and wherein the synthesis of the oligonucleotide is carried out in the presence of a compound having Formula II:   
       
         
           
           
               
               
           
         
       
       wherein SP is a solid support, W is selected from the group consisting of a carboxy linkage, an amino linkage, a carboxamido linkage, a mercaptoalkyl linkage, a succinyl linkage, an oxalyl linkage, a 3′ glycolate termini linkage, an o-nitrophenyl-1,3-propanediol linkage, an alkoxybenzylidene acetal linkage, a hydroquinone-O-0′-diacetic acid linkage, and a pentachlorophenyl-succinate linkage, and B represents a terminal chemical group from which an oligonucleotide can be synthesized. 
     
     
         2 . The method of  claim 1 , wherein said synthesis is carried out on a reaction scale of about 0.1 μmol to about 100 μmol. 
     
     
         3 . The method of  claim 1 , wherein said synthesis is carried out on a reaction scale of about 100 μmol to about 1 mmol. 
     
     
         4 . The method of  claim 1 , wherein said synthesis is carried out on a reaction scale of about 1 mmol to about 1 mol. 
     
     
         5 . The method of  claim 1 , wherein said synthesis is carried out on a reaction scale of about 1 mol to about 1000 mol. 
     
     
         6 . The method of  claim 1 , wherein said B is linked to the oligonucleotide with a 3′-5′, 3′-2′, or 3′-3′ linkage.