Gerber, Anna-BarbaraAnna-BarbaraGerberLeumann, ChristianChristianLeumann0000-0002-7996-70832024-10-142024-10-142013-05-27https://boris-portal.unibe.ch/handle/20.500.12422/112253We present the synthesis of the isobicyclo-DNA building blocks with the nucleobases A, C, G and T, as well as biophysical and biological properties of oligonucleotides derived thereof. The synthesis of the sugar part was achieved in 5 steps starting from a known intermediate of the tricyclo-DNA synthesis. Dodecamers containing single isobicyclo-thymidine incorporations, fully modified A- and T-containing sequences, and fully modified oligonucleotides containing all four bases were synthesized and characterized. Isobicyclo-DNA forms stable duplexes with natural nucleic acids with a pronounced preference for DNA over RNA as complements. The most stable duplexes, however, arise by self-pairing. Isobicyclo-DNA forms preferentially B-DNA-like duplexes with DNA and A-like duplexes with complementary RNA as determined by circular dichroism (CD) spectroscopy. Self-paired duplexes show a yet unknown structure, as judged from CD spectroscopy. Biochemical tests revealed that isobicyclo-DNA is stable in fetal bovine serum and does not elicit RNaseH activity.enDNAnucleosidesoligonucleotidesRNAserum stability500 - Science::570 - Life sciences; biology500 - Science::540 - Chemistryarticle10.7892/boris.396842361335810.1002/chem.201300487