Synthetic m3G-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 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 m3G-CAP and the artificial linker.