title: Novel isosteric, isopolar phosphonate analogs of oligonucleotides: preparation and properties.
abstract: A synthetic approach leading to novel-type modified oligothymidylates containing an isosteric, isopolar, enzyme-stable C3'-O-P-CH(2)-O-C4'' phosphonate alternative to phosphodiester internucleotide bond was elaborated. The suitable monomers were prepared from 4'-phosphonomethoxy derivatives of alpha-L-threo and beta-D-erythro-2',5'-dideoxythymidine, which were considered interesting as structurally related to nucleoside 5'-monophosphates. The phosphotriester method was applied to the automated synthesis of both homooligomeric phosphonate 15-mer chains and alternating phosphonate-phosphate constructs. The fully modified homooligomers did not hybridize while homooligomers with alternating sequences containing alpha-L-threo-configured units (but not beta-D-erythro-) showed a significant decrease in T(m) values in comparison with natural dT(15). For a comparative study, phosphodiester 4'-CH(3)-substituted oligothymidylate was synthesized and physical studies (NMR, CD, MDS modeling) were undertaken to shed more light on the changes in conformational behavior arising from the chosen structural alterations.
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: Ivan
authors.initials: I
authors.lastname: Barvík
authors.forename: Milos
authors.initials: M
authors.lastname: Budesínský
authors.forename: Ivan
authors.initials: I
authors.lastname: Rosenberg
mesh_terms: D002942:Circular Dichroism; D003198:Computer Simulation; D019281:Dimerization; D008956:Models, Chemical; D008958:Models, Molecular; D009841:Oligonucleotides / Q000737:chemistry*; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D009841:Oligonucleotides; D063065:Organophosphonates