Synthesis and duplex stability of oligodeoxyribonucleotides containing a 2′→5′-amide linkage

Abstract

2′-Deoxy-2′-α-C-carboxymethyl-3′-O-tert-butyldimethylsilyl-5′-O-dimethoxytrityluridine (11a) and the corresponding 3′-deoxy derivative 2′,3′-dideoxy-2′-α-C-carboxymethyl-5′-O-dimethoxytrityluridine (11b) have been condensed with 5′-amino-5′-deoxythymidine to prepare dinucleotide analogues (5a and 5b) which contain a 2′→5′-amide linkage. These dimer units have been incorporated into deoxynucleotide dodecamers using solid-phase phosphoramidite chemistry. Thermal melting studies show that a single 2′→5′-amide linkage in a deoxyoligonucleotide has a considerable destabilising effect on duplexes formed with both the DNA and RNA complementary sequences. Interestingly, the amide linkage has a significantly greater destabilising influence in the DNA duplexes than in the RNA hybrids.