Showing papers by "Serge L. Beaucage published in 2022"
TL;DR: In this article , a riboside phosphoramidite, carrying a 5-Ocapture linker and a 2-O-silyl ether protecting group, is incorporated into a DNA sequence during its last solid-phase synthesis cycle.
2 citations
TL;DR: Serge L. Beaucage, Supervisory Research Chemist at the Food and Drug Administration discusses his work with DNA and RNA sequences and the groundbreaking impact this technique could have.
Abstract:
Synthetic DNA and RNA sequences are currently being used as nucleic-acid-based drugs for the treatment of a plethora of human diseases under antisense and/or RNA interference therapies. This article from Serge L. Beaucage, Supervisory Research Chemist at the Food and Drug Administration discusses his work with DNA and RNA sequences and the groundbreaking impact this technique could have. Within this Q&A, Beaucage answers questions around the faults with the chemical synthesis process of DNA and RNA sequences, the challenges of purifying DNA and RNA sequences and the technologies you used to help develop this research.
TL;DR: The new isotope‐labeled phosphoramidite can therefore be applied to nuclear magnetic resonance (NMR) spectroscopy studies and can be used to make position‐specifically labeled RNAs for NMR analysis without complications from resonance overlap and scalar and dipolar couplings.
Abstract: A combined enzymatic and chemical synthesis of a 2′‐O‐cyanoethoxymethyl (CEM) protected [1′,6‐13C2, 5‐2H]‐uridine phosphoramidite is described herein. This is the first report of an atom‐specific nucleobase and ribose labeled 2′‐O‐CEM protected ribonucleoside phosphoramidite. Importantly, the CEM 2′‐OH protecting group permits the efficient solid‐phase synthesis of large (>60 nucleotides) RNAs with good yield and purity. The new isotope‐labeled phosphoramidite can therefore be applied to nuclear magnetic resonance (NMR) spectroscopy studies. Specifically, the [1′,6‐13C2, 5‐2H]‐uridine phosphoramidite can be used to make position‐specifically labeled RNAs for NMR analysis without complications from resonance overlap and scalar and dipolar couplings. © 2022 Wiley Periodicals LLC.
TL;DR: A synthetic approach consisting of a condensation reaction between 2'-O-aminoribonucleosides with ethyl pyruvate has been employed to provide stable 2'O-imino-2-methyl propanoic acid ethyl ester protecting groups to their sodium salts.
Abstract: The implementation of protecting groups for 2′‐hydroxyl function of ribonucleosides is very demanding in that synthetic RNA sequences must be highly pure to ensure the safety and efficacy of nucleic acid–based drugs for treatment of human diseases. A synthetic approach consisting of a condensation reaction between 2′‐O‐aminoribonucleosides with ethyl pyruvate has been employed to provide stable 2′‐O‐imino‐2‐methyl propanoic acid ethyl esters. Conversion of these esters to fully protected ribonucleoside phosphoramidite monomers has allowed rapid and efficient incorporation of 2′‐O‐protected ribonucleosides into RNA sequences while minimizing the formation of process‐related impurities during solid‐phase synthesis. Two chimeric 20‐mer RNA sequences have been synthesized and then exposed to a solution of sodium hydroxide to saponify the 2′‐O‐imino‐2‐methyl propanoic acid ethyl ester protecting groups to their sodium salts. When subjected to ion‐exchange conditions at 65°C and near neutral pH, fully deprotected RNA sequences are isolated without production of alkylating side‐products and/or formation of mutagenic nucleobase adducts. © 2022 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.