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Chemical synthesis of γ‐secretase activating protein using pseudoglutamines as ligation sites
Author(s) -
Harris Paul W. R.,
Squire Chris,
Young Paul G.,
Brimble Margaret A.
Publication year - 2015
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22600
Subject(s) - chemistry , native chemical ligation , cysteine , glutamine , peptide , chemical ligation , biochemistry , amino acid , lysine , sequence (biology) , chemical synthesis , oligopeptide , peptide synthesis , combinatorial chemistry , in vitro , enzyme
The chemical synthesis of analogue of a novel γ‐secretase activating protein, which may play a pivotal role in the formation of amyloid peptides, the precursor to Alzheimer's disease, is described. The linear polypeptide sequence, consisting of 121 amino acids was assembled from four unprotected peptide building blocks using a convergent ligation‐based synthesis. A strategic mutation of three glutamine residues to cysteine enabled the ligations, and the cysteines were subsequently converted to pseudoglutamines, to mimic the native glutamine. The full length unfolded protein was obtained in milligram amounts and was demonstrated to be homogeneous by liquid chromatography and mass spectrometry. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 37–45, 2015.