NMR identification of the formic acid-modified residue in Alzheimer's amyloid protein.
The beta/A4-amyloid protein (beta/A4) and many synthetic fragments of this protein have proved to be very difficult to solubilize, leading to the use of relatively harsh chemical methods, most notably, formic acid. This treatment has previously been shown to cause a covalent modification of this peptide. In this study, one- and two-dimensional NMR techniques are used to show that the nature of this covalent modification is formation of a formate ester to a serine residue. This finding is consistent with our previously reported kinetic studies of formic acid-induced modification of beta/A4 and further illustrates the potential danger of solubilizing fragments of beta/A4 in formic acid. Alternative methods of solubilization are discussed.
Klunk
W E
WE
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pennsylvania.
Xu
C J
CJ
Pettegrew
J W
JW
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D005561:Formates; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D012995:Solubility
D016229:Amyloid beta-Peptides; D005561:Formates; D009842:Oligopeptides; C030544:formic acid