Solid support for the synthesis of 3'-amino oligonucleotides

The present invention discloses novel methods and solid supports for the synthesis of 3′-amino oligonucleotides. The novel supports are based on an unsubstituted or ring-substituted hydroxymethylbenzoyl linker element wherein the hydroxymethyl group is esterified to a solid phase bound carboxylic acid and the carbonyl group is linked to an amino alcohol as an amide. Oligonucleotides are conveniently synthesized on the novel supports with no modifications in the standard phosphoramidite synthesis scheme. The ester function of the support is cleaved under the alkaline deprotection conditions for oligonucleotides to provide a free hydroxymethyl group that aids in the release of the 3′-amino oligonucleotide products with a free amino group through neighbor group participation. The free amino group of the oligonucleotides is available for further conjugation reactions to haptens, reporter groups, surfaces or other small molecules or biomolecules. The methods provided are particularly mild, do not require any modifications in standard protocols for the synthesis and deprotection of oligonucleotides, provide the 3′-amino oligonucleotides free of side products and do not introduce chiral centers to the oligonucleotides.