Clickable trimethylguanosine cap analogs modified within the triphosphate bridge: synthesis, conjugation to RNA and susceptibility to degradation
PBN-AR
Instytucja
Wydział Fizyki (Uniwersytet Warszawski)
Źródłowe zdarzenia ewaluacyjne
Informacje podstawowe
Główny język publikacji
en
Czasopismo
RSC Advances
ISSN
2046-2069
EISSN
Wydawca
DOI
URL
Rok publikacji
2016
Numer zeszytu
Strony od-do
8317-8328
Numer tomu
6
Link do pełnego tekstu
Identyfikator DOI
Liczba arkuszy
Streszczenia
Język
en
Treść
The trimethylguanosine (m3G) cap present at the 5[prime or minute] end of small nuclear RNAs (snRNAs) has been proposed as an effective nuclear localization signal (NLS) for nucleus-targeting therapeutics such as antisense oligonucleotides. To provide novel tools for studies on m3G-mediated transport and m3G degradation, we synthesized a series of novel m3G cap analogs that combine modifications potentially affecting its activity as an NLS and stability in vivo with a modification enabling simple conjugation to biomolecules. The synthesized dinucleotide m3G analogs carry a single phosphate-modification (phosphorothioate, methylenebisphosphonate or imidodiphosphate) at the selected position of the triphosphate bridge in order to increase their resistance to enzymatic cleavage and a (2-azidoethyl)-carbamoylmethyl group at the 2[prime or minute]-position of adenosine as a second nucleotide to enable conjugation to alkyne-containing biomolecules by copper catalyzed azide-alkyne cycloaddition (CuAAC). The susceptibility of m3G cap analogs to non-specific and specific degradation was studied in fetal bovine serum and in an in vitro decapping assay with hNUDT16 enzyme, respectively. The susceptibility of m3G cap analogs to hNUDT16 mediated decapping was also determined after their CuAAC-mediated conjugation to a model oligonucleotide bearing a 5[prime or minute]-alkyne group. Depending on the type and the position of introduced modifications, they modulate the susceptibility to specific and non-specific degradation of conjugated molecules to various extent, with O to NH substitution at the [small alpha]/[small beta] position providing the greatest m3G stability against hNUDT16.
Cechy publikacji
Original article
Original article presents the results of original research or experiment.
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Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:744029
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