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Caging of long oligonucleotides

December 2016. Photolabile groups (“caging groups”) are used widely in biochemical research to trigger oligonucleotide activity. Versatile applications include photoregulation of gene expression with antisense approaches, DNAzymes and ribozymes, small interfering RNAs (siRNA) and microRNAs (miRNA). The development of new caging groups now allow for one-photon activation at higher wavelength or two-photon activation with pulsed IR laser light. However, high spatiotemporal control of the investigated or regulated process is also affected by the ON/OFF triggering efficiency, which still is a challenging problem in many oligonucleotide uncaging scenarios, especially if light-control of long (>30 nt) nucleic acids has to be achieved. In a collaborative effort, scientists from the universities of Frankfurt and Bonn have now achieved photo-tethering (intrasequential circularization) of caged alkyne-modified DNA for the preparation of photoactivatable mono- and bicircularized DNA structures. They used bi- and tridentate azidolinkers as covalent tethers, which induce global bending of the DNA and block hybridization and target interaction. With this photo-tethering strategy they are able to produce photoactivatable oligonucleotides of up to 90 nt length and possibly also in the full range of DNA and RNA solid-phase synthesis. The team demonstrated that by bicircularization of the full-length C10 aptamer, formation of secondary structures and uptake of the aptamer into Burkitt's lymphoma cells was suppressed. The results suggest, that the same circularization principle could be applied for the photoregulation of arbitrary aptamer sequences, especially if some information about the folded structure is known. More...


Alexander Heckel, Institute of Organic Chemistry and Chemical Biology, Goethe University Frankfurt, Germany, heckel@uni-frankfurt.de


Seyfried P, Eiden L, Grebenovsky N, Mayer G, Heckel A. Photo-tethers for the (multi-)cyclic, conformational caging of long oligonucleotides. Angew Chem Int Edit published online 29 November 2016. dx.doi.org/10.1002/anie.201610025