title: Chemical synthesis of γ-secretase activating protein using pseudoglutamines as ligation sites.
abstract: 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.
authors.affiliation: School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland, 1010, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland, 1010, New Zealand; School of Biological Sciences, The University of Auckland, 3A Symonds Street, Auckland, 1010, New Zealand.
authors.forename: Paul W R
authors.initials: PW
authors.lastname: Harris
authors.forename: Chris
authors.initials: C
authors.lastname: Squire
authors.forename: Paul G
authors.initials: PG
authors.lastname: Young
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Brimble
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D005973:Glutamine / Q000737:chemistry*; D008026:Ligation; D010446:Peptide Fragments / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D005973:Glutamine; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimers; ligation; pseudoglutamine; γ-secretase