2′-O-propargyl oligoribonucleotides:: Synthesis and hybridisation

Fully modified oligonucleotide sequences containing 2'-O-propargylribonucleotides were synthesised on automated DNA-synthesisers using the phosphoramidite approach. A highly selective alkylation procedure was used to introduce the propargyl functionality, thereby enabling the synthesis of protected 2'-O-propargyl-3'-O-phosphoramidites, building blocks for the assembly of 2'-O-propargyl oligoribonucleotides. The suitability of phosphoramidite chemistry for the introduction of this modified nucleoside was proven using MALDI or ES mass spectrometry of the final oligomer. The 2'-O-propargyl oligoribonucleotides showed an increase in the Tm of duplexes with complementary RNA relative to the corresponding RNA homoduplex. These analogues should prove useful for a variety of antisense applications. (C) 1998 Elsevier Science Ltd. All rights reserved.