The importance of including local correlation times in the calculation of inter-proton distances from NMR measurements

Ignoring local correlation times leads to significant errors in the conformational analysis of the Glcα1-2Glcα linkage by NMR spectroscopy

Muhammad Mukram Mohamed Mackeen, Andrew Almond, Ian Cumpstey, Seth C. Enis, Eriks Kupce, Terry D. Butters, Antony J. Fairbanks, Raymond A. Dwek, Mark R. Wormald

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The experimental determination of oligosaccharide conformations has traditionally used cross-linkage 1H-1H NOE/ROEs. As relatively few NOEs are observed, to provide sufficient conformational constraints this method relies on: accurate quantification of NOE intensities (positive constraints); analysis of absent NOEs (negative constraints); and hence calculation of inter-proton distances using the two-spin approximation. We have compared the results obtained by using 1H 2D NOESY, ROESY and T-ROESY experiments at 500 and 700 MHz to determine the conformation of the terminal Glcα1-2Glcα linkage in a dodecasaccharide and a related tetrasaccharide. For the tetrasaccharide, the NOESY and ROESY spectra produced the same qualitative pattern of linkage cross-peaks but the quantitative pattern, the relative peak intensities, was different. For the dodecasaccharide, the NOESY and ROESY spectra at 500 MHz produced a different qualitative pattern of linkage cross-peaks, with fewer peaks in the NOESY spectrum. At 700 MHz, the NOESY and ROESY spectra of the dodecasaccharide produced the same qualitative pattern of peaks, but again the relative peak intensities were different. These differences are due to very significant differences in the local correlation times for different proton pairs across this glycosidic linkage. The local correlation time for each proton pair was measured using the ratio of the NOESY and T-ROESY cross-relaxation rates, leaving the NOESY and ROESY as independent data sets for calculating the inter-proton distances. The inter-proton distances calculated including the effects of differences in local correlation times give much more consistent results.

Original languageEnglish
Pages (from-to)2241-2246
Number of pages6
JournalOrganic and Biomolecular Chemistry
Volume4
Issue number11
DOIs
Publication statusPublished - 2006
Externally publishedYes

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linkages
Nuclear magnetic resonance spectroscopy
Protons
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
nuclear magnetic resonance
protons
spectroscopy
Conformations
Oligosaccharides
cross relaxation
approximation
Experiments

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)

Cite this

The importance of including local correlation times in the calculation of inter-proton distances from NMR measurements : Ignoring local correlation times leads to significant errors in the conformational analysis of the Glcα1-2Glcα linkage by NMR spectroscopy. / Mohamed Mackeen, Muhammad Mukram; Almond, Andrew; Cumpstey, Ian; Enis, Seth C.; Kupce, Eriks; Butters, Terry D.; Fairbanks, Antony J.; Dwek, Raymond A.; Wormald, Mark R.

In: Organic and Biomolecular Chemistry, Vol. 4, No. 11, 2006, p. 2241-2246.

Research output: Contribution to journalArticle

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abstract = "The experimental determination of oligosaccharide conformations has traditionally used cross-linkage 1H-1H NOE/ROEs. As relatively few NOEs are observed, to provide sufficient conformational constraints this method relies on: accurate quantification of NOE intensities (positive constraints); analysis of absent NOEs (negative constraints); and hence calculation of inter-proton distances using the two-spin approximation. We have compared the results obtained by using 1H 2D NOESY, ROESY and T-ROESY experiments at 500 and 700 MHz to determine the conformation of the terminal Glcα1-2Glcα linkage in a dodecasaccharide and a related tetrasaccharide. For the tetrasaccharide, the NOESY and ROESY spectra produced the same qualitative pattern of linkage cross-peaks but the quantitative pattern, the relative peak intensities, was different. For the dodecasaccharide, the NOESY and ROESY spectra at 500 MHz produced a different qualitative pattern of linkage cross-peaks, with fewer peaks in the NOESY spectrum. At 700 MHz, the NOESY and ROESY spectra of the dodecasaccharide produced the same qualitative pattern of peaks, but again the relative peak intensities were different. These differences are due to very significant differences in the local correlation times for different proton pairs across this glycosidic linkage. The local correlation time for each proton pair was measured using the ratio of the NOESY and T-ROESY cross-relaxation rates, leaving the NOESY and ROESY as independent data sets for calculating the inter-proton distances. The inter-proton distances calculated including the effects of differences in local correlation times give much more consistent results.",
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T1 - The importance of including local correlation times in the calculation of inter-proton distances from NMR measurements

T2 - Ignoring local correlation times leads to significant errors in the conformational analysis of the Glcα1-2Glcα linkage by NMR spectroscopy

AU - Mohamed Mackeen, Muhammad Mukram

AU - Almond, Andrew

AU - Cumpstey, Ian

AU - Enis, Seth C.

AU - Kupce, Eriks

AU - Butters, Terry D.

AU - Fairbanks, Antony J.

AU - Dwek, Raymond A.

AU - Wormald, Mark R.

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