R. Ishikawa et al., Developing model systems for the NMR study of substituent effects on the N-H center dot center dot center dot N hydrogen bond in duplex DNA, MAGN RES CH, 39, 2001, pp. S159-S165
The substitution effects on various parameters, which may influence the hyd
rogen bond strengths of Watson-Crick-type base pairs, were investigated for
DNA dodecamers containing 5-substituted-2'-deoxyuridine derivatives. In do
ing so, a series of [3-N-15]-2'-deoxyuridine derivatives, including thymidi
ne, 2'-deoxyuridine, 5-bromo-2'-deoxyuridine, 5-fluoro-2'-deoxyuridine and
5-cyano-2'-deoxyuridine, and [ul-N-15]-2'-deoxyadenosine, were synthesized
and incorporated into the DNA dodecamer, d(CGCGA* ATX* CGCG)(2), where X* a
nd A* were a [3-N-15]-2'-deoxyuridine derivative and [ul-N-15]-2'-deoxyaden
osine, respectively. The imino proton chemical shift and the spin coupling
constant between the imino proton and nitrogen [(1)J(N,H)] were measured fo
r the Watson-Crick-type A*-X* base pair of all five duplexes. The substitut
ion with an electron-withdrawing group results in downfield shift of the im
ino proton and a concomitant decrease in magnitude of the (1)J(N,H) value,
and a good, linear correlation was found between the two effects. These sub
stitution effects on the NMR parameters were linearly correlated with the p
K(a) values of the 2'-deoxyuridine derivatives and also with the theoretica
lly calculated hydrogen bond energy. The linear correlations found here ind
icate that the DNA oligomers with 5-substituted-2'-deoxyuridine provide a g
ood model to study the nature of the hydrogen bond in Watson-Crick-type bas
e pairs. Copyright (C) 2001 John Wiley & Sons, Ltd.