Artykuł w czasopiśmie
Brak miniatury
Licencja
ClosedAccessDostęp zamknięty
 

Synthesis and Evaluation of Diguanosine Cap Analogs Modified at the C8-Position by Suzuki–Miyaura Cross-Coupling: Discovery of 7-Methylguanosine-Based Molecular Rotors

Uproszczony widok
dc.abstract.enChemical modifications of the mRNA cap structure can enhance the stability, translational properties, and half-life of mRNAs, thereby altering the therapeutic properties of synthetic mRNA. However, cap structure modification is challenging because of the instability of the 5′-5′-triphosphate bridge and N7-methylguanosine. The Suzuki–Miyaura cross-coupling reaction between boronic acid and halogen compound is a mild, convenient, and potentially applicable approach for modifying biomolecules. Herein, we describe two methods to synthesize C8-modified cap structures using the Suzuki–Miyaura cross-coupling reaction. Both methods employed phosphorimidazolide chemistry to form the 5′,5′-triphosphate bridge. However, in the first method, the introduction of the modification via the Suzuki–Miyaura cross-coupling reaction at the C8 position occurs postsynthetically, at the dinucleotide level, whereas in the second method, the modification was introduced at the level of the nucleoside 5′-monophosphate, and later, the triphosphate bridge was formed. Both methods were successfully applied to incorporate six different groups (methyl, cyclopropyl, phenyl, 4-dimethylaminophenyl, 4-cyanophenyl, and 1-pyrene) into either the m7G or G moieties of the cap structure. Aromatic substituents at the C8-position of guanosine form a push–pull system that exhibits environment-sensitive fluorescence. We demonstrated that this phenomenon can be harnessed to study the interaction with cap-binding proteins, e.g., eIF4E, DcpS, Nudt16, and snurportin.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorWojtczak, Błażej
dc.contributor.authorBednarczyk, Marcelina
dc.contributor.authorJemielity, Jacek
dc.contributor.authorKowalska, Joanna
dc.contributor.authorSurynt, Piotr
dc.contributor.authorWojtczak, Anna
dc.contributor.authorSikorski, Pawel J.
dc.date.accessioned2024-01-26T09:26:27Z
dc.date.available2024-01-26T09:26:27Z
dc.date.issued2023
dc.description.financePublikacja bezkosztowa
dc.description.number11
dc.description.volume88
dc.identifier.doi10.1021/ACS.JOC.3C00126
dc.identifier.issn0022-3263
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/121284
dc.identifier.weblinkhttps://pubs.acs.org/doi/pdf/10.1021/acs.joc.3c00126
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofJournal of Organic Chemistry
dc.relation.pages6827-6846
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleSynthesis and Evaluation of Diguanosine Cap Analogs Modified at the C8-Position by Suzuki–Miyaura Cross-Coupling: Discovery of 7-Methylguanosine-Based Molecular Rotors
dc.typeJournalArticle
dspace.entity.typePublication