Synthesis and Properties of ApA Analogues with Shortened Phosphonate Internucleotide Linkage |
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Authors: | Dr Šárka Králíková Dr Miloš Buděšínský Dr Ivan Barvík Dr Milena Masojídková Dr Zdeněk Točík Ivan Rosenberg |
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Institution: | 1. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , Prague , Czech Republic;2. Charles University, Faculty of Mathematics and Physics, Institute of Physics , Prague , Czech Republic |
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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-CH2-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. |
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Keywords: | α-Hydroxy-phosphonate linkage ApA analogues phosphonate internucleotide bond modified sugar-phosphate backbone NMR conformational study MDS study |
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