Abstract
To elucidate the correlation between the structure and biological activity of 2'-substituted 2'-deoxypurinenucleoside derivatives, six ApA anologs containing 2'-fluoro-2'-deox yadenosine (dAfl) and 2'-chloro-2"-deoxyadenosine (dAcl) were synthesized and characterized by UV absorption, CD and 1H-NMR spectroscopy. The dAfl derivatives have much higher population of C3'-endo puckering than adenosine in a furanose conformational equilibrium. The dAci derivatives have. similar C3'-endo population to that of adenosine. The experimental results suggest that the dAfl-containing dimers take a stacked conformation similar to that of ApA but with larger degree of stacking. The extent of stacking decreases in the following order: dAflpdAfl> dAflpi≈ ApdAfl> ApA. The dAcl-containin dimers take a stacked conformation similar %both in the mod6 and degree to 'that of ApA. These results show that C3'-endo puckering in both residues is required for optimum stacking in a ribo-dimer. The effects of 2'-substituents on polynucleotide conformation are di, scussed.
