naa a22 4500 555285197 20190206082702.0 cr unu---uuuuu 190206s2019 xx s 000 0 eng 1860-5397 10.3762/bjoc.15.9 doi (BORIS)oai:boris.unibe.ch:123443 570 ddc 540 ddc 500 ddc Frei Sibylle Synthesis, biophysical properties, and RNase H activity of 6'-difluoro[4.3.0]bicyclo-DNA [Elektronische Daten] [Sibylle Frei, Adam Katolik, Christian Leumann] publishedVersion openAccess eu-repo Here we present the synthesis, the biophysical properties, and the RNase H profile of 6'-difluorinated [4.3.0]bicyclo-DNA (6'-diF-bc4,3-DNA). The difluorinated thymidine phosphoramidite building block was synthesized starting from an already known gem-difluorinated tricyclic glycal. This tricyclic siloxydifluorocyclopropane was converted into the [4.3.0]bicyclic nucleoside via cyclopropane ring-opening through the addition of an electrophilic iodine during the nucleosidation step followed by reduction. The gem-difluorinated bicyclic nucleoside was then converted into the corresponding phosphoramidite building block which was incorporated into oligonucleotides. Thermal denaturation experiments of these oligonucleotides hybridized to complementary DNA or RNA disclosed a significant destabilization of both duplex types (ΔTm/mod = −1.6 to −5.5 °C). However, in the DNA/RNA hybrid the amount of destabilization could be reduced by multiple insertions of the modified unit. In addition, CD spectroscopy of the oligonucleotides hybridized to RNA showed a similar structure than the natural DNA/RNA duplex. Furthermore, since the structural investigation on the nucleoside level by X-ray crystallography and ab initio calculations pointed to a furanose conformation in the southern region, a RNase H cleavage assay was conducted. This experiment revealed that the oligonucleotide containing five modified units was able to elicit the RNase H-mediated cleavage of the complementary RNA strand. Katolik Adam joint author Leumann Christian joint author Beilstein journal of organic chemistry 15, pp. 79-88 1860-5397 https://boris.unibe.ch/123443/1/1860-5397-15-9.pdf text/html WWW-Backlink auf das Repository 1 info:eu-repo/semantics/article boris PeerReviewed boris peerstatus BORIS 856 40 https://boris.unibe.ch/123443/1/1860-5397-15-9.pdf text/html WWW-Backlink auf das Repository BORIS 100 1- Frei Sibylle BORIS 700 1- Katolik Adam joint author BORIS 700 1- Leumann Christian joint author BORIS 773 0- Beilstein journal of organic chemistry 15, pp. 79-88 1860-5397 BK010053 XK010053 XK010000 BORIS BORIS BORIS info:eu-repo/semantics/article openAccess