Modification of amyloid-beta(1-40) by a protease inhibitor creates risk of error in mass spectrometric quantitation of amyloid-beta(1-42).
Matrix-assisted laser desorption mass spectrometry successfully analyzes mixed populations of amyloid-beta (Abeta) peptides, providing a profile in which changes caused by drug action are directly observed. A spectrum of Abeta immunocaptured from guinea pig brain included a novel component with monoisotopic [M+H]+ at 4511.22, close to the monoisotopic value of [M+H]+ for Abeta(1-42) of 4512.27 and overlapping and interfering with the authentic Abeta(1-42) peak. Hypothesis and experiment led to the conclusion that modification of Abeta(1-40) by the protease inhibitor aminoethylbenzenesulfonyl fluoride generates a product with monoisotopic [M+H]+ at 4511.19, and that this accounts for the interfering peak.
Conboy
James J
JJ
Pfizer Global Research and Development, Groton, CT 06340, USA.
Wood
Kathleen G
KG
Lame
Mary E
ME
Durham
Robert A
RA
Geoghegan
Kieran F
KF
D016229:Amyloid beta-Peptides / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D006168:Guinea Pigs; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013450:Sulfones / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D013450:Sulfones; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C002010:4-(2-aminoethyl)benzenesulfonylfluoride