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

摘要

Snurportin 1 is an adaptor protein that mediates the active nuclear import of uridine-rich small nuclear RNAs (U snRNA) by the importin-b 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. (C) 2015 Elsevier Ltd. All rights reserved.