title: Cleavage of vasoactive intestinal peptide at multiple sites by autoantibodies.
abstract: Vasoactive intestinal peptide (VIP) fragments generated by autoantibodies purified from the blood of two human beings were separated and sequenced. Based on the identity of these fragments, seven peptide bonds cleaved by the antibodies were identified. Six of the seven scissile bonds are clustered in the region of VIP spanning residues 14-22 and were cleaved by antibodies from both human subjects. The seventh scissile bond is located at residues 7-8 and was cleaved by antibodies from one of the subjects. The scissile bonds link amino acid residues with different size, charge, and hydrophobicity. The hydrolytic activity of the antibodies was selective in that they failed to hydrolyze polypeptides unrelated in sequence to VIP (insulin and atrial natriuretic peptide). These observations demonstrate substrate specific hydrolysis by naturally occurring antibodies and expand the range of peptide bonds hydrolyzed by these antibodies.
authors.affiliation: Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260.
authors.forename: S
authors.initials: S
authors.lastname: Paul
authors.forename: S
authors.initials: S
authors.lastname: Mei
authors.forename: B
authors.initials: B
authors.lastname: Mody
authors.forename: S H
authors.initials: SH
authors.lastname: Eklund
authors.forename: C M
authors.initials: CM
authors.lastname: Beach
authors.forename: R J
authors.initials: RJ
authors.lastname: Massey
authors.forename: F
authors.initials: F
authors.lastname: Hamel
mesh_terms: D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000276:immunology*; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006868:Hydrolysis; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008969:Molecular Sequence Data; D013379:Substrate Specificity; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D014660:Vasoactive Intestinal Peptide