SYNTHESIS AND INCORPORATION OF 5'-AMINO-5'-DEOXY-2'-O-METHYL AND 5'-MERCAPTO-5'-DEOXY-2'-O-METHYL NUCLEOSIDES INTO HAMMERHEAD RIBOZYMES

Novel 5'-amino-5'-deoxy-2'-O-methyl uridine, guanosine and adenosine 3 '-O-phosphoramidites 5, 11, and 20, as well as protected 5'-mercapto-5 '-deoxy-2'-O-methyl uridine 3'-O-phosyhoramidite 23 were synthesized f rom 2'-O-methyl nucleosides. These analogs were incorporated at the 5' -ends of hammerhead ribozymes to evaluate achiral bridging 5'-N-phosph oramidates and 5'-S-phosphorothioates as alternatives for nonbridging phosphorothioates commonly used for end stabilization against nuclease s. Oligonucleotide synthesis and deprotection conditions were optimize d for better yields of these modified ribozymes.