2'-Methylseleno modified oligoribonucleotides synthesized for X-ray crystallography

Site-specifically modified 2'-methylseleno RNA represents a valuable derivative for phasing of X-ray crystallographic data. Several successful applications in three-dimensional structure determination of nucleic acids, such as the Diels-Alder ribozyme,(1) have relied on these modifications.(2) Currently, preparation of 2'-methylseleno modified oligoribonucleotides is restricted to the 2'-O-[(triisopropylsilyl)oxy]methyl (TOM)(3,4,5) and 2'-O-tert.-butyldimethylsilyl (TBDMS) RNA synthesis methods. Recently, we have introduced synthetic routes to 2'-methylseleno phosphoramidite building blocks of all four standard nucleosides, adenosine, uridine, guanosine, cytidine, that are tailored for the 2'-O-bis(acetoxyethoxy)methyl (ACE) RNA solid-phase synthesis method.(6).