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

Madine, Jillian and Clayton, Jonathan C and Yates, Edwin A and Middleton, David A (2009) Exploiting a (13)C-labelled heparin analogue for in situ solid-state NMR investigations of peptide-glycan interactions within amyloid fibrils. Organic and Biomolecular Chemistry, 7 (11). pp. 2414-20. ISSN 1477-0520

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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 (13)C-labelled N-acetyl derivative of the GAG heparin ([(13)C-CH(3)]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 Abeta(1-40), one of the beta-amyloid polypeptides associated with Alzheimer's disease, and alpha-synuclein, the major protein component of Lewy bodies associated with Parkinson's disease. (13)C SSNMR spectra confirm the presence of [(13)C-CH(3)]NAcHep in Abeta(1-40) fibril deposits and detect dipolar couplings between the glycan and arginine R(5) at the Abeta(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.

Item Type:
Journal Article
Journal or Publication Title:
Organic and Biomolecular Chemistry
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1600/1606
Subjects:
?? ALZHEIMER DISEASEAMYLOIDAMYLOID BETA-PEPTIDESCARBON ISOTOPESHEPARINHUMANSNUCLEAR MAGNETIC RESONANCE, BIOMOLECULARPARKINSON DISEASEALPHA-SYNUCLEINBIOCHEMISTRYORGANIC CHEMISTRYPHYSICAL AND THEORETICAL CHEMISTRY ??
ID Code:
66272
Deposited By:
Deposited On:
17 Sep 2013 08:03
Refereed?:
Yes
Published?:
Published
Last Modified:
22 Sep 2023 00:21