N-{N-[2-(3,5-Difluorophenyl)acetyl]-(S)-alanyl}-(S)-phenylglycine tert-butyl ester (DAPT): An inhibitor of γ-secretase, revealing fine electronic and hydrogen-bonding features

Abstract

The title compound, C23H26F2N 2O4, is a dipeptidic inhibitor of γ-secretase, one of the enzymes involved in Alzheimer's disease. The mol-ecule adopts a compact conformation, without intra-molecular hydrogen bonds. In the crystal structure, one of the amide N atoms forms the only inter-molecular N - H⋯O hydrogen bond; the second amide N atom does not form hydrogen bonds. High-resolution synchrotron diffraction data permitted the unequivocal location and refinement without restraints of all H atoms, and the identification of the characteristic shift of the amide H atom engaged in the hydrogen bond from its ideal position, resulting in a more linear hydrogen bond. Significant residual densities for bonding electrons were revealed after the usual SHELXL refinement, and modeling of these features as additional inter-atomic scatterers (IAS) using the program PHENIX led to a significant decrease in the R factor from 0.0411 to 0.0325 and diminished the r.m.s. deviation level of noise in the final difference Fourier map from 0.063 to 0.037 e Å-3. © 2010 International Union of Crystallography.