Synthetic m 3 G-CAP attachment necessitates a minimum trinucleotide constituent to be recognised as a nuclear import signal

Achieving higher nuclear concentrations by active transport may give potent therapeutic effects at lower doses for many drugs. A method of increasing nuclear uptake is the use of naturally existing Nuclear Localization Signals (NLS) by conjugating NLS structures to the cargo. We have synthesized a s...

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Bibliographic Details
Published in:RSC advances 2016, Vol.6 (56), p.51367-51373
Main Authors: Honcharenko, M., Bestas, B., Jezowska, M., Wojtczak, B. A., Moreno, P. M. D., Romanowska, J., Bächle, S. M., Darzynkiewicz, E., Jemielity, J., Smith, C. I. E., Strömberg, R.
Format: Article
Language:English
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Summary:Achieving higher nuclear concentrations by active transport may give potent therapeutic effects at lower doses for many drugs. A method of increasing nuclear uptake is the use of naturally existing Nuclear Localization Signals (NLS) by conjugating NLS structures to the cargo. We have synthesized a set of 2,2,7-trimethylguanosine cap (m 3 G-CAP)-containing structures (and their biotin conjugates) as artificially attached analogs of a naturally found NLS. The origin of a naturally found NLS is a uridine rich, small nuclear ribonucleoprotein (U snRNP) that employs Snurportin1 as a nuclear transport protein. In this report the NLS activity of various m 3 G-CAP biotin constructs was studied. We have shown that a minimal requirement for nuclear uptake is the inclusion of a trinucleotide sequence between the m 3 G-CAP and the artificial linker.
ISSN:2046-2069
2046-2069
DOI:10.1039/C6RA09568B