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Albany 2019: 20th Conversation - Abstracts

Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Structure and Hybridization Properties of Phosphorylguanidine Oligonucleotides

Oligonucleotide analogs have been a hot topic for the past three decades because of their present and potential therapeutic applications. Recently, a new type of oligonucleotide derivatives with a modified backbone were developed - Phosphorylguanidine Oligonucleotides (PGO) (Kuprushkin et al., 2014). PGOs are unique due to the possibility of synthesis via standard automated phosphoroamidite protocol using basic set of unmodified phosphoroamidites, allowing to introduce PG modification at any position of the oligomer sequence. The high potential of the PGOs was shown in biosensors, in biological applications and in therapy (Lebedeva et al., 2015; Dmitrienko et al., 2016).

In this work, we studied the solution structure of PGOs and their complementary complexes with unmodified DNA or RNA as well as thermal stability of these complexes under conditions of different ionic strength. There were no significant differences between the CD spectra of unmodified oligonucleotides and PGOs as well as between spectra of unmodified duplexes and duplexes with one fully modified strand, indicating that PG modification insignificantly disturbs the structure of modified oligonucleotides and their duplexes with native DNA or RNA.

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Figure 1. Structure of the phosphorylguanidine modification

At high ionic strength (1 M NaCl), the thermal stability of PGO containing duplexes decreases with each added PG modification. At low ionic strength (<100 mM NaCl), complexes with one fully modified strand are more stable than the native ones. Moreover, a fully modified PGO formed highly stable duplexes with DNA or RNA even in deionized water. PGOs have sequence dependent hybridization properties and can be used for single mismatch discrimination like other native or modified oligonucleotides.

This research has been supported by the Russian Science Foundation [grant No. 18-14-00357].

References

    M. S. Kupryushkin, D. V. Pyshnyi, & D. A. Stetsenko, (2014). Phosphoryl guanidines: a new type of nucleic acid analogues. Acta Naturae , 6(4) , 116–118.

    N. A. Lebedeva, R. O. Anarbaev, M. S. Kupryushkin, N. I.Rechkunova, D. V. Pyshnyi, D. A. Stetsenko,; O. I. Lavrik, Design of a New Fluorescent Oligonucleotide-Based Assay for a Highly Specific Real-Time Detection of Apurinic/Apyrimidinic Site Cleavage by Tyrosyl-DNA Phosphodiesterase 1. (2015) Bioconjug Chem, 26 (10), 2046-53.

    E.V. Dmitrienko, O. Naumova, B. Fomin, M.S. Kupryushkin, A.I. Volkova, N.V. Amirkhanov, D. Semenov, I.A. Pyshnaya,; D.V. Pyshnyi, Surface modification of SOI-FET sensors for label-free and specific detection of short RNA analyte. (2016) Nanomedicine (Lond), 11 (16), 2073-82.

Alexander A. Lomzov
Victor M. Golyshev
Evgeniya S. Dyudeeva
Maksim S. Kupryushkin
Dmitriy V. Pyshnyi

Institute of Chemical Biology and Fundamental Medicine SB RAS
Novosibirsk State University
Novosibirsk 630090, Russia

Ph: +7-383-363-5134
Fx: +7-383-363-5153
Email: lomzov@niboch.nsc.ru