Synthesis and Pairing Properties of Oligodeoxynucleotides Containing Bicyclo-RNA and Bicyclo-ANA Modifications

The synthesis of the ribo­(bc-rT)- and arabino­(bc-araT)-version
of bicyclothymidine (bc-dT) has been achieved. A conformational analysis
by X-ray and/or 1H NMR spectroscopy on the corresponding
3′,5′-benzyl-protected nucleosides featured a rigid
C(2′)-endo conformation for the furanose ring, irrespective
of the configuration of the OH group at C(2′). The conformation
of the carbocyclic ring in these nucleosides was found to be less
defined and thus more flexible. Both nucleosides were converted into
the corresponding phosphoramidites and incorporated into oligodeoxynucleotides
by standard DNA chemistry. Tm-data of
duplexes with cDNA and RNA revealed that a bc-rT unit strongly destabilized
duplexes with cDNA and RNA by 6–8 °C/mod, while bc-araT
was almost Tm neutral. A rationale based
on a previous structure of a bc-DNA mini duplex suggests that the
strong destabilization caused by a bc-rT unit arises from unfavorable
steric interactions of the equatorial 2′-OH group with the
sugar residue of the 3′-neighboring nucleotide unit.