Peer-reviewedCC BY-NCRSC advances
An activator-free method for the synthesis of nucleotide 5′–5′ triphosphate mRNA capping agent
- 1Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR) 8 Biomedical Grove, #07-01 Neuros Building Singapore 138665 Republic of Singapore [email protected].
- 2Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR) 60 Biopolis Street, #02-01 Genome Building Singapore 138672 Republic of Singapore.
- 3Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR) 20 Biopolis Way, #06-01 Centros Building Singapore 138668 Republic of Singapore.
Abstract
The traditional synthesis of nucleotide 5'-5' triphosphate linkages involves a "2 + 1" phosphate coupling mediated by a large excess of metal salts, where the salt removal is a labor and waste-intensive step. We have omitted the metal salts from this reaction by modulating the solubility and reactivity of the monophosphate coupling partner using a precise combination of the reaction solvent and the paired cation. This resulted in simplified downstream purification, where the amount of waste generated was reduced by over 60% throughout the whole process. We have demonstrated this synthetic approach on ARCA, an mRNA 5'-capping agent. Both the chemical purity of the product and its performance in mRNA was comparable to commercial samples.
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BibTeX
@article{tam2026activatorfree,
title = {{An activator-free method for the synthesis of nucleotide 5′–5′ triphosphate mRNA capping agent}},
author = {Eric Tam and Viktor Barát and Tzuen Yih Saw and Kuo-Chieh Liao and Yue Wan and Shuwen Chen and Ying Swan Ho and Yee Hwee Lim},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra08498b},
url = {https://europepmc.org/article/PMC/PMC13717511},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - An activator-free method for the synthesis of nucleotide 5′–5′ triphosphate mRNA capping agent
AU - Eric Tam
AU - Viktor Barát
AU - Tzuen Yih Saw
AU - Kuo-Chieh Liao
AU - Yue Wan
AU - Shuwen Chen
AU - Ying Swan Ho
AU - Yee Hwee Lim
PY - 2026
DA - 2026/10/29
JO - RSC advances
DO - 10.1039/d6ra08498b
UR - https://europepmc.org/article/PMC/PMC13717511
AB - The traditional synthesis of nucleotide 5'-5' triphosphate linkages involves a "2 + 1" phosphate coupling mediated by a large excess of metal salts, where the salt removal is a labor and waste-intensive step. We have omitted the metal salts from this reaction by modulating the solubility and reactivity of the monophosphate coupling partner using a precise combination of the reaction solvent and the paired cation. This resulted in simplified downstream purification, where the amount of waste generated was reduced by over 60% throughout the whole process. We have demonstrated this synthetic approach on ARCA, an mRNA 5'-capping agent. Both the chemical purity of the product and its performance in mRNA was comparable to commercial samples.
SN - 2046-2069
ER -