Hydrolysis of the amyloid β-peptide (Aβ) 1–40 between Asp23–Val24 produces non-aggregating fragments. An electrospray mass spectrometric study

✍ Scribed by Waltteri Hosia; William J. Griffiths; Jan Johansson

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 108 KB
• Volume: 40
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.732

✦ Synopsis

Abstract

The aggregation of full‐length (residues 1–40) amyloid β‐peptide (Aβ) 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, Aβ(1–40) at 140 µM concentration aggregates with apparent first‐order kinetics. Under acidic conditions Aβ(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~^18^O showed incorporation of ^18^O in fragment Aβ(1–23), confirming that the Asp23–Val24 peptide bond had been hydrolyzed. Incubation of synthetic Aβ(1–23) and Aβ(24–40) peptides with Aβ(1–40) showed that Aβ(24–40) remained in solution for several months, that Aβ(1–23) partly disappeared from solution, whereas Aβ(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 Aβ(1–40). These data support previous studies showing that the region of Aβ encompassing residues 16–24 is necessary for aggregation into amyloid fibrils. Copyright © 2005 John Wiley & Sons, Ltd.