Diastereomers of a mono-substituted phosphoryl guanidine trideoxyribonucleotide: Isolation and properties.

Diastereomers of a mono-substituted phosphoryl guanidine trideoxyribonucleotide: Isolation and properties.
Biochem Biophys Res Commun. 2019 Apr 15;:
Authors: Lomzov AA, Kupryushkin MS, Shernyukov AV, Nekrasov MD, Dovydenko IS, Stetsenko DA, Pyshnyi DV
Abstract
Recently, a new type of nucleic acid analogues with modified phosphate group, namely, phosphoryl guanidine oligonucleotides, has been described. In the present work, we assess the difference between diastereomers of a mono-substituted phosphoryl guanidine oligonucleotide and analyze their resistance to nuclease digestion. Individual diastereomers ('fast' and 'slow') of a trideoxynucleotide d (TpCp*A) were isolated by reverse-phase HPLC. Snake venom phosphodiesterase digestion showed that the native trideoxynucleotide was fully degraded after 30 min, whereas both 'fast' and 'slow' diastereomers of d (TpCp*A) were not completely digested even after 7 days. UV and CD spectra revealed similarities in the structure of the diastereomers. Structural analysis by 1D and 2D NMR spectroscopy also uncovered significant similarity in the properties of Rp and Sp diastereomers. Structural analysis of nuclear Overhauser effect spectroscopy (NOESY) data and restrained molecular dynamics methods showed very flexible single-stranded oligonucleotide structures. Detailed computational analysis of restraint penalty energies via restrained molecular dynamics simulations with the 2D NMR interproton d...

Source: Biochemical and Biophysical Research communications - April 14, 2019 Category: Biochemistry Authors: Lomzov AA, Kupryushkin MS, Shernyukov AV, Nekrasov MD, Dovydenko IS, Stetsenko DA, Pyshnyi DV Tags: Biochem Biophys Res Commun Source Type: research