How to find the optimal partner--studies of snurportin 1 interactions with U snRNA 5' TMG-cap analogues containing modified 2-amino group of 7-methylguanosine.

Karolina Piecyk, Anna Niedzwiecka, Aleksandra Ferenc-Mrozek, Maciej Lukaszewicz, Edward Darzynkiewicz, Marzena Jankowska-Anyszka

Bioorganic & medicinal chemistry 2015 Aug 1

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Snurportin 1 is an adaptor protein that mediates the active nuclear import of uridine-rich small nuclear RNAs (U snRNA) by the importin-β receptor pathway. Its cellular activity influences the overall transport yield of small ribonucleoprotein complexes containing N(2),N(2),7-trimethylguanosine (TMG) capped U snRNA. So far little is still known about structural requirements related to molecular recognition of the trimethylguanosine moiety by snurportin in solution. Since these interactions are of a great biomedical importance, we synthesized a series of new 7-methylguanosine cap analogues with extended substituents at the exocyclic 2-amino group to gain a deeper insight into how the TMG-cap is adapted into the snurportin cap-binding pocket. Prepared chemical tools were applied in binding assays using emission spectroscopy. Surprisingly, our results revealed strict selectivity of snurportin towards the TMG-cap structure that relied mainly on its structural stiffness and compactness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Citation

Karolina Piecyk, Anna Niedzwiecka, Aleksandra Ferenc-Mrozek, Maciej Lukaszewicz, Edward Darzynkiewicz, Marzena Jankowska-Anyszka. How to find the optimal partner--studies of snurportin 1 interactions with U snRNA 5' TMG-cap analogues containing modified 2-amino group of 7-methylguanosine. Bioorganic & medicinal chemistry. 2015 Aug 1;23(15):4660-8