Novel nucleic acid analogs with a chimeric phosphinate / phosphate backbone; synthesis and biophysical properties

Abstract

Novel analogs of acyclic nucleosides based on a bis-hydroxymethylphosphinic acid (BHPA) backbone were incorporated into a thymidine-containing DNA strand by phosphoramidite methodology. The physicochemical properties of these constructs were evaluated. Melting temperature measurements demonstrate that chimeric oligomers with a phosphinate / phosphate backbone possess lower binding affinity towards complementary single stranded templates and slightly higher binding affinity towards double stranded DNA, as compared to non-modified reference oligomers. The polyanionic oligomers containing BHPA abasic residue were also synthesized by the same methodology. These oligomers show low cytotoxic activity toward HUVEC and HeLa cell lines and, as expected, are resistant to nucleolytic degradation at the modification site.