Abstract
A complete series of the 2'-5' and 3'-5' regioisomeric types of r(ApA) and 2'-d(ApA) analogues with the a-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 chirality on the 5'-carbon atom of the modified internucleotide linkage, each regioisomeric type of ApA dimer is split into epimeric pairs.
The role of 5'-hydroxyl of the a-hydroxy-phosphonate moiety during hybridization was studied. NMR conformational study on modified sugar-phosphate backbone, along with hybridization measurements and MDS, revealed remarkable differences in the stability of complexes with polyU, depending on the 5'-carbon atom configuration.