Alzheimer's beta-amyloid protein is covalently modified when dissolved in formic acid.
beta-Amyloid protein is a major protein component of neuritic plaques in the brain of Alzheimer's disease patients. A major advance in understanding the molecular biology of Alzheimer's disease came with the purification and sequencing of this protein. Because beta-amyloid protein is very insoluble, extreme conditions such as 88% formic acid were commonly used to dissolve its fibrils. We now report that 88% formic acid covalently modifies beta-amyloid protein fragments, probably by the formation of a formate ester to a serine in the protein. The t1/2 of the formylation is approximately 3.5 h, and the t1/2 for hydrolysis of the formylated peptide is much longer, being 9.9 h in water and 66 h in HPLC eluant. This suggests that if formic acid is used in the purification of beta-amyloid protein or peptide fragments of this protein, it is likely that some formylated peptide will be present in subsequent studies. Although unrecognized modification of a protein is inherently undesirable, it is uncertain what effects this formylation will have on ensuing studies. Certainly, investigations into the immunologic, physical, and physiologic properties of beta-amyloid protein could be influenced.
Klunk
W E
WE
Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania.
Pettegrew
J W
JW
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides; D004355:Drug Stability; D005561:Formates / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data
D000682:Amyloid; D016229:Amyloid beta-Peptides; D005561:Formates; C030544:formic acid