title: Synthesis and properties of ApA analogues with shortened phosphonate internucleotide linkage.
abstract: A complete series of the 2 '-5 ' and 3 '-5 ' regioisomeric types of r(ApA) and 2 '-d(ApA) analogues with the α-hydroxy-phosphonate C3 '-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 '-carbon atom of the modified internucleotide linkage bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is split into epimeric pairs. To examine the role of the 5 '-hydroxyl of the α-hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues with 3 '(2 ')-O-P-CH(2)-C4 ″ linkage lacking the 5 '-hydroxyl were synthesized. Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the modified sugar-phosphate backbone, along with the hybridization measurements, revealed remarkable differences in the stability of complexes with polyU, depending on the 5 '-carbon atom configuration. Potential usefulness of the α-hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.
authors: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors: Sárka
authors: S
authors: Králíková
authors: Miloš
authors: M
authors: Buděšínský
authors: Ivan
authors: I
authors: Barvík
authors: Milena
authors: M
authors: Masojídková
authors: Zdeněk
authors: Z
authors: Točík
authors: Ivan
authors: I
authors: Rosenberg
mesh_terms: D060326:Chemistry Techniques, Synthetic; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry*; D011072:Poly U / Q000737:chemistry*
chemical_list: D063065:Organophosphonates; D011072:Poly U