title: Hydrolysis of the amyloid beta-peptide (A beta) 1-40 between Asp23-Val24 produces non-aggregating fragments. An electrospray mass spectrometric study.
abstract: The aggregation of full-length (residues 1-40) amyloid beta-peptide (A beta) and fragments corresponding to residues 1-23 and 24-40 was studied by electrospray mass spectrometry, using gramicidin as a non-aggregating reference. Following a lag period, A beta(1-40) at 140 microM concentration aggregates with apparent first-order kinetics. Under acidic conditions A beta(1-40) undergoes spontaneous cleavage between Asp23-Val24 and to a lesser extent also at two other Asp-X motifs. Incubation in acidic H(2)18O showed incorporation of 18O in fragment A beta(1-23), confirming that the Asp23-Val24 peptide bond had been hydrolyzed. Incubation of synthetic A beta(1-23) and A beta(24-40) peptides with A beta(1-40) showed that A beta(24-40) remained in solution for several months, that A beta(1-23) partly disappeared from solution, whereas A beta(1-40) completely disappeared. Further, treatment of sedimentable aggregates formed after co-incubation of the three peptides with hexafluoro-2-propanol or formic acid recovered the intensity of A beta(1-40). These data support previous studies showing that the region of A beta encompassing residues 16-24 is necessary for aggregation into amyloid fibrils.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Waltteri
authors.initials: W
authors.lastname: Hosia
authors.forename: William J
authors.initials: WJ
authors.lastname: Griffiths
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry; D006868:Hydrolysis; D010446:Peptide Fragments / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors; D014633:Valine / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D001224:Aspartic Acid; D014633:Valine