2'-DEOXY-7-(HYDROXYMETHYL)-7-DEAZAADENOSINE - A NEW ANALOG TO MODEL STRUCTURAL WATER IN THE MAJOR GROOVE OF DNA

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.