Issue 3, 2024

Synthesis of short DNA and RNA fragments by resonant acoustic mixing (RAM)

Abstract

We demonstrate the first use of Resonant Acoustic Mixing (RAM) without bulk solvent for the synthesis of short oligonucleotide fragments. Using the modified H-phosphonate approach, DNA, RNA, and 2′-modified nucleotides were successfully coupled to 3′-protected nucleosides in high yields (63–92%) while reducing solvent volume by 90%. In addition to synthesizing protected phosphodiester (PO) dimers and trimers, we also synthesized protected phosphorothioate (PS) dimers in good yields (63–65%). Using phosphoramidite chemistry, we were similarly able to reduce the solvent volume by 90% while coupling DNA phosphoramidites (58–92%) and RNA phosphoramidites (55–95%) with 3′-protected nucleosides in high yields followed by traditional oxidation with iodine in solution. Both strategies were successfully scaled up to multi-gram quantities which was facilitated by the use of RAM, offering the potential for larger scale-up, up to hundreds of kilograms continuously.

Graphical abstract: Synthesis of short DNA and RNA fragments by resonant acoustic mixing (RAM)

Supplementary files

Article information

Article type
Paper
Submitted
11 Feb 2024
Accepted
24 Mar 2024
First published
28 Mar 2024
This article is Open Access
Creative Commons BY-NC license

RSC Mechanochem., 2024,1, 244-249

Synthesis of short DNA and RNA fragments by resonant acoustic mixing (RAM)

J. D. Thorpe, J. Marlyn, S. G. Koenig and M. J. Damha, RSC Mechanochem., 2024, 1, 244 DOI: 10.1039/D4MR00009A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements