title: Redox potential dependence of peptide structure studied using surface enhanced Raman spectroscopy.
abstract: We describe a novel surface enhanced Raman spectroscopy (SERS) sensing approach utilizing modified gold nanoshells and demonstrate its application to analysis of critical redox-potential dependent changes in antigen structure that are implicated in the initiation of a human autoimmune disease. In Goodpasture's disease, an autoimmune reaction is thought to arise from incomplete proteolysis of the autoantigen, α3(IV)NC1(67-85) by proteases including Cathepsin D. We have used SERS to study conformational changes in the antigen that correlate with its oxidation state and to show that the antigen must be in the reduced state in order to undergo proteolysis. Our results demonstrate that a redox potential of ∼-200 mV was sufficient for reduction and subsequent productive processing of the antigenic fragment α3(IV)NC1(67-85). Moreover, we demonstrate that the peptide bonds subsequently cleaved by Cathepsisn D can be identified by comparison with a SERS library of short synthetic peptides.
authors.affiliation: EaSTCHEM School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JJ, UK. mochsenk@ed.ac.uk
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ochsenkühn
authors.forename: Joanna A
authors.initials: JA
authors.lastname: Borek
authors.forename: Richard
authors.initials: R
authors.lastname: Phelps
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Campbell
mesh_terms: D001324:Autoantigens / Q000737:chemistry*; D002236:Carbohydrate Conformation; D024141:Collagen Type IV / Q000737:chemistry*; D006046:Gold / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D036103:Nanotechnology; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013499:Surface Properties
chemical_list: D001324:Autoantigens; D024141:Collagen Type IV; D010455:Peptides; C057112:type IV collagen alpha3 chain; D006046:Gold