title: Conformational evaluation of labeled C3'-O-P-(13)CH(2)-O-C4'' phosphonate internucleotide linkage, a phosphodiester isostere.
abstract: Modified internucleotide linkage featuring the C3'-O-P-CH(2)-O-C4'' phosphonate grouping as an isosteric alternative to the phosphodiester C3'-O-P-O-CH(2)-C4'' bond was studied in order to learn more on its stereochemical arrangement, which we showed earlier to be of prime importance for the properties of the respective oligonucleotide analogues. Two approaches were pursued: First, the attempt to prepare the model dinucleoside phosphonate with (13)C-labeled CH(2) group present in the modified internucleotide linkage that would allow for a more detailed evaluation of the linkage conformation by NMR spectroscopy. Second, the use of ab initio calculations along with molecular dynamics (MD) simulations in order to observe the most populated conformations and specify main structural elements governing the conformational preferences. To deal with the former aim, a novel synthesis of key labeled reagent (CH(3)O)(2)P(O)(13)CH(2)OH for dimer preparation had to be elaborated using aqueous (13)C-formaldehyde. The results from both approaches were compared and found consistent.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, 16610 Prague 6, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Tocík
authors.forename: Milos
authors.initials: M
authors.lastname: Budesínský
authors.forename: Ivan
authors.initials: I
authors.lastname: Barvík
authors.forename: Ivan
authors.initials: I
authors.lastname: Rosenberg
mesh_terms: D003198:Computer Simulation; D019281:Dimerization; D004952:Esters / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009711:Nucleotides / Q000737:chemistry*; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry*; D013194:Staining and Labeling; D013237:Stereoisomerism
chemical_list: D004952:Esters; D009711:Nucleotides; D063065:Organophosphonates