1. Synthesis and Properties of ApA Analogues with Shortened Phosphonate Internucleotide Linkage.
- Author
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Králíková, Šárka, Buděšínský, Miloš, Barvík, Ivan, Masojídková, Milena, Točík, Zdeněk, and Rosenberg, Ivan
- Subjects
PHOSPHONATES ,NUCLEOTIDES ,PHOSPHODIESTERASES ,COMPLEX compounds ,ORGANIC synthesis ,NUCLEAR magnetic resonance spectroscopy ,CONFORMATIONAL analysis - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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