Next Article in Journal
Analytical Problems with Preparation of Paraspinal Tissues from Patients with Spinal Fusion for Analysis of Titanium
Next Article in Special Issue
Chemistry of Peptide-Oligonucleotide Conjugates: A Review
Previous Article in Journal
Activation of Hair Cell Growth Factors by Linoleic Acid in Malva verticillata Seed
Previous Article in Special Issue
Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences
Article

A Versatile Solid-Phase Approach to the Synthesis of Oligonucleotide Conjugates with Biodegradable Hydrazone Linker

1
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
2
UMR Genetique Moleculaire, Genomique, Microbiologie (GMGM), Strasbourg University—CNRS, 67084 Strasbourg, France
*
Author to whom correspondence should be addressed.
Academic Editors: Harri Lönnberg and Roger Strömberg
Molecules 2021, 26(8), 2119; https://doi.org/10.3390/molecules26082119
Received: 5 March 2021 / Revised: 3 April 2021 / Accepted: 4 April 2021 / Published: 7 April 2021
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugate II)
One of the ways to efficiently deliver various drugs, including therapeutic nucleic acids, into the cells is conjugating them with different transport ligands via labile or stable bonds. A convenient solid-phase approach for the synthesis of 5′-conjugates of oligonucleotides with biodegradable pH-sensitive hydrazone covalent bonds is proposed in this article. The approach relies on introducing a hydrazide of the ligand under aqueous/organic media to a fully protected support-bound oligonucleotide containing aldehyde function at the 5′-end. We demonstrated the proof-of-principle of this approach by synthesizing 5′-lipophilic (e.g., cholesterol and α-tocopherol) conjugates of modified siRNA and non-coding RNAs imported into mitochondria (antireplicative RNAs and guide RNAs for Mito-CRISPR/system). The developed method has the potential to be extended for the synthesis of pH-sensitive conjugates of oligonucleotides of different types (ribo-, deoxyribo-, 2′-O-methylribo-, and others) with ligands of different nature. View Full-Text
Keywords: solid-phase 5′-functionalization; lipophilic conjugates of oligonucleotides; pH-sensitive hydrazone covalent bonds; siRNA; mitochondrial antireplicative and guide RNAs solid-phase 5′-functionalization; lipophilic conjugates of oligonucleotides; pH-sensitive hydrazone covalent bonds; siRNA; mitochondrial antireplicative and guide RNAs
Show Figures

Figure 1

MDPI and ACS Style

Meschaninova, M.I.; Entelis, N.S.; Chernolovskaya, E.L.; Venyaminova, A.G. A Versatile Solid-Phase Approach to the Synthesis of Oligonucleotide Conjugates with Biodegradable Hydrazone Linker. Molecules 2021, 26, 2119. https://doi.org/10.3390/molecules26082119

AMA Style

Meschaninova MI, Entelis NS, Chernolovskaya EL, Venyaminova AG. A Versatile Solid-Phase Approach to the Synthesis of Oligonucleotide Conjugates with Biodegradable Hydrazone Linker. Molecules. 2021; 26(8):2119. https://doi.org/10.3390/molecules26082119

Chicago/Turabian Style

Meschaninova, Mariya I., Nina S. Entelis, Elena L. Chernolovskaya, and Alya G. Venyaminova. 2021. "A Versatile Solid-Phase Approach to the Synthesis of Oligonucleotide Conjugates with Biodegradable Hydrazone Linker" Molecules 26, no. 8: 2119. https://doi.org/10.3390/molecules26082119

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop