title: Synthesis of amine- and thiol-modified nucleoside phosphoramidites for site-specific introduction of biophysical probes into RNA.
abstract: For studies of RNA structure, folding, and catalysis, site-specific modifications are typically introduced by solid-phase synthesis of RNA oligonucleotides using nucleoside phosphoramidites. Here, we report the preparation of two complete series of RNA nucleoside phosphoramidites; each has an appropriately protected amine or thiol functional group. The first series includes each of the four common RNA nucleotides, U, C, A, and G, with a 2'-(2-aminoethoxy)-2'-deoxy substitution (i.e., a primary amino group tethered to the 2'-oxygen by a two-carbon linker). The second series encompasses the four common RNA nucleotides, each with the analogous 2'-(2-mercaptoethoxy)-2'-deoxy substitution (i.e., a tethered 2'-thiol). The amines are useful for acylation and reductive amination reactions, and the thiols participate in displacement and oxidative cross-linking reactions, among other likely applications. The new phosphoramidites will be particularly valuable for enabling site-specific introduction of biophysical probes and constraints into RNA.
authors.affiliation: Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801, USA.
authors.forename: Shengxi
authors.initials: S
authors.lastname: Jin
authors.forename: Chandrasekhar V
authors.initials: CV
authors.lastname: Miduturu
authors.forename: David C
authors.initials: DC
authors.lastname: McKinney
authors.forename: Scott K
authors.initials: SK
authors.lastname: Silverman
mesh_terms: D000577:Amides / Q000138:chemical synthesis*; D000588:Amines / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis*; D063088:Phosphoramides; D010756:Phosphoric Acids / Q000138:chemical synthesis*; D012313:RNA / Q000138:chemical synthesis / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000577:Amides; D000588:Amines; D009841:Oligonucleotides; D063088:Phosphoramides; D010756:Phosphoric Acids; D013438:Sulfhydryl Compounds; C005438:phosphoramide; D012313:RNA