Structure of an 11-mer DNA duplex containing the carbocyclic nucleotide analog: 2 '-deoxyaristeromycin

2'-deoxyaristeromycin (dAr) is a nucleoside analogue that is resistant to t he action of DNA glycosylases. High-resolution NMR spectroscopy and molecul ar dynamics simulations were used to determine the three-dimensional struct ure of an Il-mer DNA containing a single dAr.T base pair at its center. Ana lysis of the spectra revealed the existence of a right-handed duplex in sol ution, stabilized by Watson-Crick hydrogen bonding and base-stacking intera ctions. The carbocyclic sugar adopted a Cl'-Exo conformation and sugars of the 3'-flanking base pair had puckers in the O4'-endo range. The dAr.T base pair was mildly propeller twisted, and the dAr analogue showed a positive roll with the 3'-flanking base. Our findings indicate that the observed res istance of dAr-containing oligodeoxynucleotides to the catalytic action of DNA glycosylases relates to its electronic properties rather than structure , and validate the use of dAr and related carbocyclic nucleoside analogues for biological and structure/function relationship studies.