TY - JOUR

T1 - Effects of Phosphoryl Guanidine Modification of Phosphate Residues on the Structure and Hybridization of Oligodeoxyribonucleotides

AU - Golyshev, Victor M.

AU - Pyshnyi, Dmitrii V.

AU - Lomzov, Alexander A.

N1 - Funding Information: V.M.G. acknowledges financial support from RFBR [19-34-90127] for the experimental and computational experiments. D.V.P. and A.A.L. acknowledge financial support from the basic budgetary funding [AAAA-A17-117020210021-7] for the oligonucleotide synthesis and data analysis. D.V.P. is a cofounder and shareholder of NOOGENE LLC, a company focused on the synthesis of PGO analogs. Publisher Copyright: © 2021 American Chemical Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/3/25

Y1 - 2021/3/25

N2 - Phosphoryl guanidine oligonucleotides (PGOs) are promising tools for biological research and development of biosensors and therapeutics. We performed structural and hybridization analyses of octa-, deca-, and dodecamers with all phosphate residues modified by 1,3-dimethylimidazolidine-2-imine moieties. Similarity of the B-form double helix between native and modified duplexes was noted. In PGO duplexes, we detected a decrease in the proportion of C2'-endo and an increased proportion of C1'-exo sugar conformations of the modified chain. Applicability of the two-state model to denaturation transition of all studied duplexes was proved for the first time. Sequence-dependent effects of this modification on hybridization properties were observed. The thermal stability of PGO complexes is almost native at 100 mM NaCl and slightly increases with decreasing ionic strength. An increase in water activity and dramatic changes in interaction with cations and in solvation of PGOs and their duplexes were noted, resulting in slight elevation of the melting temperature after an ionic-strength decrease from 1 M NaCl down to deionized water. Decreased binding of sodium ions and decreased water solvation were documented for PGOs and their duplexes. In contrast to DNA, the PGO duplex formation leads to a release of several cations. The water shell is significantly more disordered near PGOs and their complexes. Nevertheless, changes in solvation during the formation of native and PGO complexes are similar and indicate that it is possible to develop models for predictive calculations of the thermodynamic properties of phosphoryl guanidine oligomers. Our results may help devise an approach for the rational design of PGOs as novel improved molecular probes and tools for many modern methods involving oligonucleotides.

AB - Phosphoryl guanidine oligonucleotides (PGOs) are promising tools for biological research and development of biosensors and therapeutics. We performed structural and hybridization analyses of octa-, deca-, and dodecamers with all phosphate residues modified by 1,3-dimethylimidazolidine-2-imine moieties. Similarity of the B-form double helix between native and modified duplexes was noted. In PGO duplexes, we detected a decrease in the proportion of C2'-endo and an increased proportion of C1'-exo sugar conformations of the modified chain. Applicability of the two-state model to denaturation transition of all studied duplexes was proved for the first time. Sequence-dependent effects of this modification on hybridization properties were observed. The thermal stability of PGO complexes is almost native at 100 mM NaCl and slightly increases with decreasing ionic strength. An increase in water activity and dramatic changes in interaction with cations and in solvation of PGOs and their duplexes were noted, resulting in slight elevation of the melting temperature after an ionic-strength decrease from 1 M NaCl down to deionized water. Decreased binding of sodium ions and decreased water solvation were documented for PGOs and their duplexes. In contrast to DNA, the PGO duplex formation leads to a release of several cations. The water shell is significantly more disordered near PGOs and their complexes. Nevertheless, changes in solvation during the formation of native and PGO complexes are similar and indicate that it is possible to develop models for predictive calculations of the thermodynamic properties of phosphoryl guanidine oligomers. Our results may help devise an approach for the rational design of PGOs as novel improved molecular probes and tools for many modern methods involving oligonucleotides.

UR - http://www.scopus.com/inward/record.url?scp=85103607261&partnerID=8YFLogxK

U2 - 10.1021/acs.jpcb.0c10214

DO - 10.1021/acs.jpcb.0c10214

M3 - Article

C2 - 33724825

AN - SCOPUS:85103607261

VL - 125

SP - 2841

EP - 2855

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 11

ER -