Synthesis and duplex stability of oligodeoxyribonucleotides containing a 2'-> 5 '-amide linkage

2'-Deoxy-2'-alpha-C-carboxymethyl-3'-O-tert-butyldimethylsiyl-5'-O-dimethox yltrityluridine (11a) and the corresponding 3'-deoxy derivative 2',3'-dideo xy-2'-alpha-C-carboxymethyl-5'-O-dimethyoxytrityluridine (11b) have been co ndensed with 5'-amino-5'-deoxythymidine to prepare dinucleotide analogues ( 5a and 5b) which contain a 2'-->5'-amide linkage. These dimer units have be en incorporated into deoxynucleotide dodecamers using solid-phase phosphora midite chemistry Thermal melting studies show that a single 2'-->5'-amide l inkage in a deoxyoligonucleotide has a considerable destabilising effect on duplexes formed with both the DNA and RNA complementary sequences; Interes tingly, the amide linkage has a significantly greater destabilising influen ce in the DNA duplexes than in he RNA hybrids.