S. Smirnov et al., Structure of an 11-mer DNA duplex containing the carbocyclic nucleotide analog: 2 '-deoxyaristeromycin, J BIO STRUC, 17(6), 2000, pp. 981-991
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.