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Issue 11, 2009
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Exploiting a 13C-labelled heparin analogue for in situ solid-state NMR investigations of peptide-glycan interactions within amyloid fibrils

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Abstract

Pathological amyloid deposits are mixtures of polypeptides and non-proteinaceous species including heparan sulfate proteoglycans and glycosaminoglycans (GAGs). We describe a procedure in which a 13C-labelled N-acetyl derivative of the GAG heparin ([13C-CH3]NAcHep) serves as a useful probe for the analysis of GAG-protein interactions in amyloid using solid-state nuclear magnetic resonance (SSNMR) spectroscopy. NAcHep emulates heparin by enhancing aggregation and altering the fibril morphology of 1–40, one of the β-amyloid polypeptides associated with Alzheimer's disease, and α-synuclein, the major protein component of Lewy bodies associated with Parkinson's disease. 13C SSNMR spectra confirm the presence of [13C-CH3]NAcHep in 1–40 fibril deposits and detect dipolar couplings between the glycan and arginine R5 at the 1–40 N-terminus, suggesting that the two species are intimately mixed at the molecular level. This procedure provides a foundation for further extensive investigations of polypeptide-glycan interactions within amyloid fibrils.

Graphical abstract: Exploiting a 13C-labelled heparin analogue for in situ solid-state NMR investigations of peptide-glycan interactions within amyloid fibrils

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Publication details

The article was received on 20 Nov 2008, accepted on 25 Feb 2009 and first published on 31 Mar 2009


Article type: Paper
DOI: 10.1039/B820808E
Citation: Org. Biomol. Chem., 2009,7, 2414-2420
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    Exploiting a 13C-labelled heparin analogue for in situ solid-state NMR investigations of peptide-glycan interactions within amyloid fibrils

    J. Madine, J. C. Clayton, E. A. Yates and D. A. Middleton, Org. Biomol. Chem., 2009, 7, 2414
    DOI: 10.1039/B820808E

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