title: Synthesis of oligoribonucleotides with phosphonate-modified linkages.
abstract: Solid phase synthesis of phosphonate-modified oligoribonucleotides using 2'-O-benzoyloxymethoxymethyl protected monomers is presented in both 3'→5' and 5'→3' directions. Hybridisation properties and enzymatic stability of oligoribonucleotides modified by regioisomeric 3'- and 5'-phosphonate linkages are evaluated. The introduction of the 5'-phosphonate units resulted in moderate destabilisation of the RNA/RNA duplexes (ΔT(m)-1.8 °C/mod.), whereas the introduction of the 3'-phosphonate units resulted in considerable destabilisation of the duplexes (ΔT(m)-5.7 °C/mod.). Molecular dynamics simulations have been used to explain this behaviour. Both types of phosphonate linkages exhibited remarkable resistance in the presence of ribonuclease A, phosphodiesterase I and phosphodiesterase II.
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2, 16610, Prague, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Páv
authors.forename: Ivana
authors.initials: I
authors.lastname: Košiová
authors.forename: Ivan
authors.initials: I
authors.lastname: Barvík
authors.forename: Radek
authors.initials: R
authors.lastname: Pohl
authors.forename: Miloš
authors.initials: M
authors.lastname: Buděšínský
authors.forename: Ivan
authors.initials: I
authors.lastname: Rosenberg
mesh_terms: D005092:Exonucleases / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D043264:Phosphodiesterase I / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D060327:Solid-Phase Synthesis Techniques
chemical_list: D009843:Oligoribonucleotides; D063065:Organophosphonates; D005092:Exonucleases; C022650:spleen exonuclease; D012259:Ribonuclease, Pancreatic; D043264:Phosphodiesterase I