Covalent cross-linking within supramolecular peptide structures

George W. Preston, Sheena E. Radford, Alison E. Ashcroft, Andrew J. Wilson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

β-Sheet peptide nanostructures (e.g., amyloid fibrils) are recognized as important entities in biological systems and as functional materials in their own right. Their unique physical properties and architectural complexity, however, present a challenge for structure determination at atomic resolution. Covalent cross-linking and mass spectrometry are appealing methods for this endeavor because, potentially, a large amount of information can be extracted from a small sample in a single experiment. Previously, we described preliminary studies on the use of a photoreactive diazirine-containing amino acid to cross-link peptide monomers in nanostructures, together with the integrated separation and analysis of the products using ion mobility spectrometry coupled to conventional mass spectrometry. Here, a pH-switchable system (Aβ16-22, a sequence from the amyloid-β peptide) was used to examine cross-linking chemistry in morphologically distinct supramolecular structures containing, or entirely composed of, diazirine-functionalized peptides. We examine the relationship between cross-linker chemistry, covalent cross-links (identified using chemical derivatization and tandem mass spectrometry), and noncovalent structure, and report differences in the site of cross-linking that can only be explained by supramolecular templating. The results demonstrate the applicability of the approach for obtaining structural restraints in ordered supramolecular assemblies, provided that a considered evaluation of the cross-linked products is undertaken.

Original languageEnglish
Pages (from-to)6790-6797
Number of pages8
JournalAnalytical Chemistry
Volume84
Issue number15
DOIs
Publication statusPublished - 7 Aug 2012

ASJC Scopus subject areas

  • Analytical Chemistry

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