Cross-linking of a synthetic partial-length (1–28) peptide of the Alzheimer β/A4 amyloid protein by transglutaminase

Abstract

Cerebral deposits of β/A4 amyloid protein is a pathologic sign of Alzheimer's disease. A synthetic partial-length (1–28) peptide of this protein contains one glutamine and two lysine residues. Here we show that this peptide can be a substrate of transglutaminase, which catalyzes cross-linking between glutamine and lysine residues in peptides, by demonstrating the formation of multimeric peptides due to the action of this enzyme. A modified (LyS 28 to l-norleucine) version of the synthetic peptide was also cross-linked, but another modified version (Lys 16 to l-norleucine) was very poorly cross-linked, indicating that Lys 16 is involved exclusively in the cross-linking of the partial-length peptide catalyzed by transglutaminase.