Solid Phase Conjugation Chemistry: Use of Alloc as a Protecting Group for 2′-Aminolinker Containing Oligonucleotides

Abstract

The drug properties of antisense and antigene oligonucleotides can he enhanced by strategic positioning of ligands capable of ameliorating these properties.^1,2 Certain ligands may improve the cellular delivery of oligomers and increase their affinity for the target gene and resistance to nucleases. The 2′-O-position is an attractive modification site.³ Oligonucleotides possessing the 2′-O-akyl modifications exhibit higher chemical stability under depurination conditions, higher stability to enzymatic cleavage by both endo- and exonucleases, and increased affinity for target mRNA. In addition, they form highly stable triple helices. Thus they promise to be versatile compounds in controlling gene expression by antisense and antigene technologies.