We describe the synthesis and pairing properties of the novel DNA analogue 7',5'-bicyclo(bc)-DNA. In this analogue, the point of attachment of the connecting phosphodiester group is switched from the 3' to the 7' position of the underlying bicyclic sugar unit and is thus in a topological position that is inaccessible in natural DNA. The corresponding phosphoramidite building blocks carrying all natural nucleobases were synthesized and incorporated into oligonucleotides. From T(m) experiments of duplexes with complementary DNA and RNA we find that single modifications are generally well tolerated with some variability as to the nature of the nucleobase. Fully modified oligonucleotides show low affinity for RNA and DNA complements. However, they form antiparallel homo-duplexes with similar thermal stability as DNA. CD spectra of the homo-duplexes show distinct changes in the helix conformation compared to natural DNA. A conformational analysis at the ab initio level of the mononucleosides revealed two minimal energy structures which primarily deviate in the conformation of the cyclopentane ring. Molecular dynamics simulation of a 7',5'-bc-DNA homo-duplex revealed a right-handed structure with a smaller helical rise and a significantly wider minor groove compared to DNA. Interestingly, this duplex is characterized by an atypical, alternating 6'-endo/6'-exo conformational pattern of consecutive nucleotides which seems to be responsible for the poor binding to natural nucleic acids.