The distinct conformational preferences observed for the pentofuranosyl moieties in various 3’-substituted 2’,3’-dideoxythymidine derivatives are closely related to the strength of the 3’-gauche effect, which is directly dictated by the electronegativity of the 3’-substituent. The efficiency of the 3’-gauche effect can now be quantitatively calculated with the help of simple linear calibration curves that correlate the gauche effect enthalpy (Delta H(GE)degrees and the group electronegativity (X) of the 3’-substituent.