Structural compatibility of novel nucleotide modifications with shortened linkages designed for antigene/antisense therapy

Abstract

Hybridization properties of oligonucleotides with isopolar shortened internucleotide linkage were studied by using a model system of polyuridylic acid and diadenosine monophosphate analogs with the modified linkage. Analysis of the spectral sets obtained for four ApA analogues and natural ApA provided amounts of formed pseudo-triplexes and their Raman spectra.

S-ApCOHA(2 -5 ) a R-ApCOHA(3 -5 ) analogs triplex formation even exceed the ApA. This is reached, however, by a more feasible prolongation of the pseudo-chain, while the stability constant for the initiation step is significantly lower.

Raman spectra of the complexes showed that for both of the above analogs the structural compatibility with the natural nucleic acid chain is decreased, because of the distorted position of one adenine residue.