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Acta Crystallogr C. 2010 Dec;66(Pt 12):o585-8. Epub 2010 Nov 6.

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.

Czerwinski A, Valenzuela F, Afonine P, Dauter M, Dauter Z.

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Peptides International Inc., 11621 Electron Drive, Louisville, KY 40299, USA.

Abstract

The title compound, C(23)H(26)F(2)N(2)O(4), is a dipeptidic inhibitor of γ-secretase, one of the enzymes involved in Alzheimer's disease. The molecule adopts a compact conformation, without intramolecular hydrogen bonds. In the crystal structure, one of the amide N atoms forms the only intermolecular 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 interatomic 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).

PMID:: 21123889; [PubMed - indexed for MEDLINE]
PMCID:: PMC3014104

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