title: Modification of amyloid-beta(1-40) by a protease inhibitor creates risk of error in mass spectrometric quantitation of amyloid-beta(1-42).
abstract: 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.
authors.affiliation: Pfizer Global Research and Development, Groton, CT 06340, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Conboy
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Wood
authors.forename: Mary E
authors.initials: ME
authors.lastname: Lame
authors.forename: Robert A
authors.initials: RA
authors.lastname: Durham
authors.forename: Kieran F
authors.initials: KF
authors.lastname: Geoghegan
mesh_terms: 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*
chemical_list: 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