research highlights

NUCLEIC ACIDS cells, therefore therapies based on exogenous Next, the team tested the efficacy of the An interfering delivery siRNA require a mechanism to transfer for releasing siRNA inside Angew. Chem. Int. Ed. http://dx.doi.org/10.1002/ siRNA across the cell membrane. Although the cell. Experiments with cancer cell lines anie.201406764 (2014) a variety of viral, lipid and vectors showed that siRNA could be effectively have been developed, delivery efficiency is delivered, and that the production of both siRNA often low and can vary depending on the type messenger RNA and protein targets could of cell being targeted. be reduced. Further experiments showed Ling Peng from Aix-Marseille University, that siRNA could also be delivered into France, and co-workers have developed a both stem cells and primary cells. In a final nanocarrier for delivering siRNA into cells demonstration, the team showed that the siRNA/dendrimer that is based on an amphiphilic dendrimer. siRNA/dendrimer nanoparticles could reduce Dendrimersome complexes In water the dendrimer self-assembles into messenger RNA and protein expression levels vesicle-like dendrimersomes; however, on in a prostate cancer mouse model. This led addition of siRNA the dendrimersomes to the effective inhibition of tumour growth rearrange into smaller micelle structures. without discernible . RJ This rearrangement increases the positively charged surface area of the micelle and ASYMMETRIC CATALYSIS

© 2014 WILEY thereby increases the potential for stabilizing Not so boring boron interactions between the dendrimer Nature 513, 367–374 (2014) Short interfering RNAs (siRNAs) are and negatively charged siRNA. These double-stranded pieces of RNA that can act interactions induce the micelles and siRNA to Multicomponent synthesis — the coupling as antiviral agents or can be used to reduce condense and form colloidal nanoparticles. of multiple reagents in one pot — is an the expression of specific genes via RNA Computational studies confirm the adaptive attractive option for synthetic chemists interference pathways. The potential for rearrangement and assembly mechanism, when the creation of structurally complex altering complex biological systems makes and initial experiments established that the target compounds in meaningful quantities them interesting therapeutic candidates. nanoparticles could protect the siRNA from is difficult via typical linear chemical However, siRNA is not easily taken up by degradation and were rapidly taken up by cells. transformations. Although there have

CLICK

Two-faced copper J. Am. Chem. Soc. 136, 13590–13593 (2014)

The very high conversions reached by ‘click’ Cu reactions under mild conditions make them (MeCN) CuBF very popular for modular syntheses — and 4 4 none more so than the copper-catalysed H H azide–alkyne cycloaddition (CuAAC). To O N O N avoid the use of a copper catalyst, it has Cat. TBTA R1N also been shown that cyclooctyn substrates O 3 O

can be used in a strain-promoted azide– R2 N alkyne cycloaddition (SPAAC) reaction Cu N N

that is often exploited for bioorthogonal Aq. NH3 labelling. However, if a contains R2N both a cyclooctyne and a terminal alkyne, N N 3 N N H H any azide added for a cycloaddition will O N N R1 O N N R1 be swiftly mopped up by the cyclooctyne O O — and protecting groups for cyclooctynes are scarce. that was unreactive towards free azides. The which a copper-binding suitable for Now, Suguru Yoshida and Takamitsu Cu–alkyne complex could be disrupted by the CuAAC catalysis was added with an excess Hosoya, leading a team from Tokyo Medical addition of aqueous ammonia, regenerating of azide in order to react with a terminal and Dental University and the Tokyo Institute the cyclooctyne and making it available for alkyne on the same molecule. Addition of Technology, have exploited a copper salt to strain-promoted azide–alkyne cycloaddition. of aqueous ammonia unmasked the both protect a cyclooctyne, and then catalyse Using copper as both a cyclooctyne, which reacted immediately the CuAAC reaction on a terminal alkyne in and catalyst, a CuAAC reaction followed by a with the remaining azide. It was also shown the same molecule. Yoshida, Hosoya and SPAAC reaction were carried out on a single that two different azides could be used in co-workers screened a variety of coinage molecule in a one-pot, three-step process. the CuAAC and SPAAC reaction steps. The metal salts, and found that addition of a slight An excess of copper salt was used — one combined protection–reaction strategy

excess of (MeCN)4CuBF4 quantitatively equivalent for protection and the remaining opens the door for modular click syntheses formed an isolable octyne–Cu complex pre-dissolved for the CuAAC step — after of cyclooctyne-containing compounds. CH

946 NATURE CHEMISTRY | VOL 6 | NOVEMBER 2014 | www.nature.com/naturechemistry

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