The conformation of carbohydrates

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The conformation of carbohydrates

• What can scalar coupling constants (nJ) tell us?

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Tetrasaccharide ProteinHeparin Basic
Fibroblast Growth Factor
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Conformation of theglycosidic linkage
jH (H1-C1-O4-C4)
yH (C1-O4-C4-H4)
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Properties of the glycosidic linkage

• Stereoelectronic (exo-anomeric-) effects
  influence the jH torsion
• The yH torsion is determined by steric factors
• Both jH and yH are known to prefer a single
  conformation with varying flexibility

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Difficulties

• Two consecutive torsion angles are needed to
  define the conformation
• No 3JHH values related to the glycosidic torsion
• NOE distances depend on both torsion angles

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Not a unique problem!
A similar situation exists in peptides
yi (Ni-Cai-Ci-Ni1)
ji (Ci-1-Ni-Cai-Ci)
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Solution Heteronuclear Js
ji
yi

• 3JCi-1,Hai
• 3JCi-1,Ci
• 3JCi-1,Cbi
• 3JHNi,Hai
• 3JHNi,Ci
• 3JHNi,Cbi

• 3JHa,Ni1
• 3JCbi,Ni1

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Couplings across glycosidic linkage
jH
yH

• 3JH1,Cn
• 3JC2,Cn

• 3JC1,Hn
• 3JC1,Cn-1
• 3JC1,Cn1

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Couplings related to jH
3JC2,C4
3JH1,C4
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Couplings related to yH
3JC1,C3
3JC1,H4
3JC1,C5
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Example bDGal(1?3)bDGalOMe
3JC1,C40.5 Hz
3JC1,H3 4.0 Hz
3JC1,C22.6 Hz
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Torsion angle dependence of couplings across O3-C3
3JC1,H3
Coupling constant (Hz)
3JC1,C2
3JC1,C4
yH (deg.)
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Deviation between calculated and experimental vs
yH
3JC1,H3
3JC1,C2
Error (Hz)
3JC1,C4
yH (deg)
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RMS deviation vs yH
possible structures
RMS (Hz)
yH (deg)
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Gaussian distribution
syn-conformer
anti-conformer
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Lorentzian distribution
syn-conformer
anti-conformer
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Conclusion

• Using two or more 3J values a much more detailed
  picture of the conformation of disaccharides
  emerges
• Some ambiguities (e.g. syn?anti) can not be
  resolved by 3J values alone

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Acknowledgements

• Prof. A. S. Serianni
• Michael Vercillo
• Omicron Biochemicals
• Knut och Alice Wallenbergs stiftelse