NMR AND MOLECULAR MODELING CHARACTERIZATION OF HIV-1 PROTEASE INHIBITORS - DIFUNCTIONAL ENOLS OF N-PROTECTED PHENYLALANINE

The three-dimensional structure of five HIV protease inhibitors of the N-tert-butoxycarbonylphenylalanyl enol family have been investigated by NMR and molecular modeling. Complete H-1 and C-13 chemical shift as signments were obtained. Both the E and Z forms were observable, the p ercentage of Z form being of the order of 20-30%. Coupling constant me asurements indicated that the NH-CH alpha dihedral angles are differen t for the E and Z forms. Docking calculations with the HIV protease yi eld minimal energies which correlate with their experimental inhibitio n constants. (C) 1997 Elsevier Science Ltd.