Jk. Rockhill et al., 2'-DEOXY-7-(HYDROXYMETHYL)-7-DEAZAADENOSINE - A NEW ANALOG TO MODEL STRUCTURAL WATER IN THE MAJOR GROOVE OF DNA, Journal of the American Chemical Society, 118(42), 1996, pp. 10065-10068
A novel deoxynucleoside, 2'-deoxy-7-(hydroxymethyl)-7-deazaadenosine,
was synthesized with the intent of using the analogue to mimic the rol
e of ''structural'' waters in the major groove of DNA. The target comp
ound was synthesized in four steps starting from erythro-pentofuranosy
l)pyrrole-3,4-dicarbonitrile. The structure was characterized by X-ray
diffraction and proton NMR spectroscopic analyses. The crystal struct
ure shows an intramolecular hydrogen bond between an amino proton on N
6 and the oxygen of the hydroxymethyl group. When superimposed onto pa
rticular adenines in the structure of the tryptophan (trp) repressor/o
perator complex, the analogue places the oxygen of the hydroxymethyl g
roup very near the oxygen contributed by the water in the protein/DNA
complex. This analogue may be useful for probing the role of structura
l waters in other specific protein/DNA complexes and in DNA bending.