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

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

Journal

Biochemical and Biophysical Research Communications
ISSN: 0006-291X , E-ISSN: 1090-2104

Output data

Year: 2019, Volume: 513, Number: 4, Pages: 807-811 Pages count : 5 DOI: 10.1016/j.bbrc.2019.04.024

Tags

Phosphoryl guanidine oligonucleotide; Diastereomer assignment; Phosphodiesterase digestion assay; Spatial structure

Authors

Lomzov Alexander A. ^1,3 , Kupryushkin Maxim S. ¹ , Shernyukov Andrey V. ^2,3 , Nekrasov Mikhail D. ³ , Dovydenko Ilya S. ¹ , Stetsenko Dmitry A. ^1,3 , Pyshnyi Dmitrii V. ^1,3

Affiliations

1	(Данные Web of science) RAS, SB, Inst Chem Biol & Fundamental Med, 8 Lavrentiev Ave, Novosibirsk 630090, Russia
2	(Данные Web of science) RAS, SB, NN Vorozhtsov Novosibirsk Inst Organ Chem, 9 Lavrentiev Ave, Novosibirsk 630090, Russia
3	(Данные Web of science) Novosibirsk State Univ, 2 Pirogova St, Novosibirsk 630090, Russia

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 Over-hauser 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 distance data allowed us to conclude that most likely, the 'fast' isomer is the Sp diastereomer, and the 'slow' isomer is the Rp diastereomer. (C) 2019 Elsevier Inc. All rights reserved.

Lomzov A.A. , Kupryushkin M.S. , Shernyukov A.V. , Nekrasov M.D. , Dovydenko I.S. , Stetsenko D.A. , Pyshnyi D.V.
Diastereomers of a mono-substituted phosphoryl guanidine trideoxyribonucleotide: Isolation and properties
Biochemical and Biophysical Research Communications. 2019. V.513. N4. P.807-811. DOI: 10.1016/j.bbrc.2019.04.024 WOS Scopus РИНЦ OpenAlex

Published print:

Jun 1, 2019

Web of science:	WOS:000468856400007
Scopus:	2-s2.0-85064217496
Elibrary:	38709229
OpenAlex:	W2937760808

DB	Citing
Web of science	24
Scopus	21
Elibrary	25
OpenAlex	25