Abstract
Nucleic acids (DNA and RNA) have widespread applications in medicinal chemistry as well as in material sciences. It is possible to increase these applications and their efficacy by introducing chemical modifications. Such modifications bearing sequences are designated as artificial nucleic acids. Serinol Nucleic Acids (SNA) are artificial nucleic acids which differ from the natural DNA/RNA in their backbone structure. Their backbone contains serinol (2-amino-1,3-propanediol) monomers instead of ribose units. The serinol monomer must be in a suitable form for any DNA synthesizer to incorporate it into the DNA sequence. In that scope, the alcohol group at one end of the serinol monomer must be selectively protected. For DNA or RNA synthesis the nucleosides' alcohol groups are usually protected with 4,4’-dimethoxytrityl (DMTr) groups. Thus protecting serinol's alcohol group with DMTr is an important step in artificial nucleic acid synthesis. However, traditional dimethoxytritylation reactions are consuming significant amounts of time and solvent. We therefore wondered if microwave heating could be applied for serinol protection reactions. Our experimental results give first evidence that microwave heating could be possibly used to protect serinol with 4,4'-dimethoxytrityl group and further optimization is necessary.
References
- [1] Moccia M., Pascucci B., Saviano M., Cerasa M.T., Terzidis M.A., Chatgilialoglu C., Masi A., Advances in Nucleic Acid Research: Exploring the Potential of Oligonucleotides for Therapeutic Applications and Biological Studies, Int. J. Mol. Sci., 25 (2024) 146.
- [2] Silverman S.K., DNA as a Versatile Chemical Component for Catalysis, Encoding, and Stereocontrol, Angew Chem Int Ed Engl., 49 (2010) 7180-7201.
- [3] Wang F., Li P., Chu H.C., Lo P.K., Nucleic Acids and Their Analogues for Biomedical Applications, Biosensors (Basel), 12 (2) (2022) 93.
- [4] Fàbrega C., Aviñó A., Eritja R., Chemical Modifications in Nucleic Acids for Therapeutic and Diagnostic Applications, Chem. Rec., 22 (2022) e202100270.
- [5] Bell N.M., Micklefield J., Chemical Modification of Oligonucleotides for Therapeutic, Bioanalytical and other Applications, ChemBioChem, 10 (2009) 2691-2703.
- [6] Bege M., Borbás A., The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides, Pharmaceuticals (Basel), 15 (8) (2022) 909.
- [7] Seeman N.C., An overview of structural DNA nanotechnology, Mol. Biotechnol., 37 (2007) 246–57.
- [8] Nielsen P.E., Peptide nucleic acids (PNA) in chemical biology and drug discovery, Chemistry & Biodiversity, 7(4) (2010) 786-804.
- [9] Asanuma H., Kamiya Y., Kashida H., Murayama K., Xeno nucleic acids (XNAs) having non-ribose scaffolds with unique supramolecular properties, Chem Comm, 58 (25) (2022) 3993-4004.
- [10] Kanlidere Z., Template-Directed Incorporation of Functional Molecules into DNA, ChemBioChem, 24 (2023) e202200554.
- [11] Kashida H., Murayama K., Asanuma H., Acyclic artificial nucleic acids with phosphodiester bonds exhibit unique functions, Polym J., 48 (2016) 781–786.
- [12] Benhida R., Devys M., Fourrey J-L., Lecubin F., Sun J-S., Incorporation of serinol derived acyclic nucleoside analogues into oligonucleotides: Influence on duplex and triplex formation, Tetrahedron Letters, 39(34) (1998) 6167-6170.
- [13] Kashida H., Murayama K., Toda T., Asanuma H., Control of the chirality and helicity of oligomers of serinol nucleic acid (SNA) by sequence design, Angew Chem Int Ed Engl. 50 (6) (2011) 1285-1288.
- [14] Kumara V., Kesavan V., Acyclic butyl nucleic acid (BuNA): a novel scaffold for A-switch, RSC Adv., 3 (2013) 19330-19340.
- [15] Zhang L., Peritz A., Meggers E., A Simple Glycol Nucleic Acid, Journal of the American Chemical Society, 127 (12) (2005) 4174-4175.
- [16] Murayama K., Kashida H., Asanuma H., The Use of Serinol Nucleic Acids as Ultrasensitive Molecular Beacons, Methods Mol Biol., 1973 (2019) 261-279.
- [17] Houser T. J., McCarville M. E., Biftu T., Kinetics of the Thermal Decomposition of Pyridine in a Flow System, Int. J. Chem. Kinet., 12 (8) (1980) 555–568.
- [18] Klute C.H., Walters W.D., The Thermal Decomposition of Tetrahydrofuran, Journal of the American Chemical Society, 68 (3) (1946) 506-511.
- [19] Lifshitz A., Tamburu C., Thermal decomposition of acetonitrile. Kinetic modeling, Int. J. Chem. Kinet., 30 (1998) 341–347.
- [20] Alfonsi K., Colberg J., Dunn P. J., Fevig T., Jennings S., Johnson T. A., Kleine H. P., Knight C., Nagy M. A., Perry D. A., Stefaniak M., Green chemistry tools to influence a medicinal chemistry and research chemistry based organisation, Green Chem., 10 (2008) 31-36.
Details
| Primary Language | English |
|---|---|
| Subjects | Organic Chemical Synthesis, Organic Chemistry (Other) |
| Journal Section | Natural Sciences |
| Authors | |
| Publication Date | September 30, 2025 |
| Submission Date | February 21, 2025 |
| Acceptance Date | April 24, 2025 |
| Published in Issue | Year 2025 Volume: 46 Issue: 3 |
