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A Versatile Solid-Phase Approach to the Synthesis of Oligonucleotide Conjugates with Biodegradable Hydrazone Linker.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2021 Apr 07; Vol. 26 (8). Date of Electronic Publication: 2021 Apr 07. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Chemistry Techniques, Synthetic
Drug Stability
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
Molecular Structure
Oligonucleotides chemical synthesis
Biocompatible Materials chemistry
Hydrazones chemistry
Oligonucleotides chemistry
Solid-Phase Synthesis Techniques methods
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 26
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 33917095
- Full Text :
- https://doi.org/10.3390/molecules26082119