A novel route for preparing 5[prime or minute] cap mimics and capped RNAs: phosphate-modified cap analogues obtained via click chemistry
PBN-AR
Instytucja
Wydział Fizyki (Uniwersytet Warszawski)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Chemical Science (40pkt w roku publikacji)
ISSN
2041-6520
EISSN
2041-6539
Wydawca
ROYAL SOC CHEMISTRY
DOI
URL
Rok publikacji
2017
Numer zeszytu
Strony od-do
260-267
Numer tomu
8
Identyfikator DOI
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Streszczenia
Język
en
Treść
The significant biological role of the mRNA 5[prime or minute] cap in translation initiation makes it an interesting subject for chemical modifications aimed at producing useful tools for the selective modulation of intercellular processes and development of novel therapeutic interventions. However, traditional approaches to the chemical synthesis of cap analogues are time-consuming and labour-intensive, which impedes the development of novel compounds and their applications. Here, we explore a different approach for synthesizing 5[prime or minute] cap mimics, making use of click chemistry (CuAAC) to combine two mononucleotide units and yield a novel class of dinucleotide cap analogues containing a triazole ring within the oligophosphate chain. As a result, we synthesized a library of 36 mRNA cap analogues differing in the location of the triazole ring, the polyphosphate chain length, and the type of linkers joining the phosphate and the triazole moieties. After biochemical evaluation, we identified two analogues that, when incorporated into mRNA, produced transcripts translated with efficiency similar to compounds unmodified in the oligophosphate bridge obtained by traditional synthesis. Moreover, we demonstrated that the triazole-modified cap structures can be generated at the RNA 5[prime or minute] end using two alternative capping strategies: either the typical co-transcriptional approach, or a new post-transcriptional approach based on CuAAC. Our findings open new possibilities for developing chemically modified mRNAs for research and therapeutic applications, including RNA-based vaccinations.
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Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:800359
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