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
- Peptides International Inc., 11621 Electron Drive, Louisville, KY 40299 (United States)
- Lawrence Berkeley National Laboratory, One Cyclotron Road, Building 64R0121, Berkeley, CA 94720 (United States)
- Basic Research Program, SAIC-Frederick Inc., Synchrotron Radiation Research Section, MCL, NCI, Argonne National Laboratory, Biosciences Division, Building 202, Argonne, IL 60439 (United States)
- Synchrotron Radiation Research Section, MCL, NCI, Argonne National Laboratory, Biosciences Division, Building 202, Argonne, IL 60439 (United States)
The title compound, C{sub 23}H{sub 26}F{sub 2}N{sub 2}O{sub 4}, is a dipeptidic inhibitor of γ-secretase, one of the enzymes involved in Alzheimer’s dis@@ease. 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{sup −3}.
- OSTI ID:
- 22347678
- Journal Information:
- Acta Crystallographica. Section C, Crystal Structure Communications, Vol. 66, Issue Pt 12; Other Information: PMCID: PMC3014104; PMID: 21123889; PUBLISHER-ID: mx3037; OAI: oai:pubmedcentral.nih.gov:3014104; Copyright (c) International Union of Crystallography 2010; This is an open-access article distributed under the terms described at http://journals.iucr.org/services/termsofuse.html.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0108-2701
- Country of Publication:
- Denmark
- Language:
- English
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