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

Chemistry

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https://doi.org/10.1039/b820808e
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Keywords

Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Carbon Isotopes, Heparin, Humans, Nuclear Magnetic Resonance, Biomolecular, Parkinson Disease, alpha-Synuclein

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Exploiting a (13)C-labelled heparin analogue for in situ solid-state NMR investigations of peptide-glycan interactions within amyloid fibrils. / Madine, Jillian; Clayton, Jonathan C; Yates, Edwin A et al.
In: Organic and Biomolecular Chemistry , Vol. 7, No. 11, 07.06.2009, p. 2414-20.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Author

Madine, Jillian ; Clayton, Jonathan C ; Yates, Edwin A et al. / Exploiting a (13)C-labelled heparin analogue for in situ solid-state NMR investigations of peptide-glycan interactions within amyloid fibrils. In: Organic and Biomolecular Chemistry . 2009 ; Vol. 7, No. 11. pp. 2414-20.

Bibtex

@article{c634305087f94652b77d50074f78eef5,

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

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.",

keywords = "Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Carbon Isotopes, Heparin, Humans, Nuclear Magnetic Resonance, Biomolecular, Parkinson Disease, alpha-Synuclein",

author = "Jillian Madine and Clayton, {Jonathan C} and Yates, {Edwin A} and Middleton, {David A}",

year = "2009",

month = jun,

day = "7",

doi = "10.1039/b820808e",

language = "English",

volume = "7",

pages = "2414--20",

journal = "Organic and Biomolecular Chemistry ",

issn = "1477-0520",

publisher = "Royal Society of Chemistry",

number = "11",

}

RIS

TY - JOUR

T1 - Exploiting a (13)C-labelled heparin analogue for in situ solid-state NMR investigations of peptide-glycan interactions within amyloid fibrils

AU - Madine, Jillian

AU - Clayton, Jonathan C

AU - Yates, Edwin A

AU - Middleton, David A

PY - 2009/6/7

Y1 - 2009/6/7

N2 - 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.

AB - 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.

KW - Alzheimer Disease

KW - Amyloid

KW - Amyloid beta-Peptides

KW - Carbon Isotopes

KW - Heparin

KW - Humans

KW - Nuclear Magnetic Resonance, Biomolecular

KW - Parkinson Disease

KW - alpha-Synuclein

U2 - 10.1039/b820808e

DO - 10.1039/b820808e

M3 - Journal article

C2 - 19462052

VL - 7

SP - 2414

EP - 2420

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 11

ER -

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