期刊
RSC ADVANCES
卷 2, 期 33, 页码 12949-12962出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2ra22345g
关键词
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资金
- Swedish Science Research Council
- Magnus Bergvalls Foundation
- Torsten and Ragnar Soderberg Foundation
- Duchenne Parent Project
- Swedish Foundation for Strategic Research
- VINNOVA
- European Council [ITN-2008-238679]
The RNA components of small nuclear ribonucleoproteins (U snRNPs) possess a characteristic 5'-terminal 2,2,7-trimethyl-guanosine CAP structure (m(3)G-CAP). This cap is an important component of the nuclear localization signal of U snRNPs. Here we report synthesis of four m(3)G-CAP constructs and the effective attachment of these onto oligonucleotides (ONs) using Cu(I) [3 + 2] cycloaddition (click chemistry''). The four constructs (1-4, Fig. 1) are equipped with a handle that in principle allows for universal conjugation to any cargo and differ in their complexity starting from m(3)GpppA((linker)) to m(3)GpppA((OMe))U((OMe))A((linker)) that resembles the native m(3)G-CAP followed by the 2'-O-methylated sequence AUA. The four m(3)G-CAP containing constructs are equipped with an azide linker and by taking advantage of initial attachment of a novel activated triple bond donor p-aminomethyltoluic acid (PATA) to ONs on solid support we were able to synthesize novel bioconjugates equipped with different constructs carrying the m(3)G-CAP Nuclear Localisation Signal (NLS) for the investigation of nuclear delivery.
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