An Intramolecular O-N Migration Reaction on Gold Surfaces: Toward the Preparation of Well-Defined Amyloid Surfaces

Amyloids are a family of self-aggregating proteins implicated in various central nervous system disorders, including Alzheimers disease (AD). It is thought that prefibrillar soluble forms of amyloid peptides, including oligomers, may be the main pathogenic factor in AD. Herein we describe the fabrication of well-defined, functionalized, monomeric beta-amyloid peptide surfaces for studying protein-protein interactions. We first prepared a nonaggregating analogue of the beta-amyloid peptide and then attached it to a gold surface covered with a self-assembled monolayer (SAM) of alkanethiols. After attachment, the native form of the beta-amyloid peptide (A beta 40) was obtained by surface-level intramolecular O-N migration. The surface was characterized by atomic force microscopy (AFM) and self-assembled monolayer for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (SAMDI-TOF MS). The interaction between the surface-bound A beta 40 and monoclonal anti-A beta 40 antibody was tracked by AFM and chemiluminescence, which revealed that the A beta 40 was attached mainly in its monomeric form and that the protein-protein complex was assembled on the surface. Last, we used a proteomics approach to demonstrate the specificity of the A beta 40-functionalized surface in surface-binding experiments employing serum amyloid P (SAP) and bovine serum albumin (BSA).