Rational Design of Peptide Ligands Against a Glycolipid by NMR Studies

  • Wenyong Tong
  • Tara Sprules
  • Kalle Gehring
  • H. Uri SaragoviEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 928)


Ganglioside GD2 is a cell surface glycosphingolipid that is targeted clinically for cancer diagnosis, prognosis, and therapy. The conformations of free GD2 and of GD2 bound to anti-GD2 mAb 3F8 were resolved by saturation transfer difference nuclear magnetic resonance and molecular modeling. Then small molecule cyclic peptide ligands that bind to GD2 selectively were designed, and shown to affect GD2-mediated signal transduction. The solution structure of the GD2-bound conformation of the peptide ligands showed an induced-fit binding mechanism. This work furthers the concept of rationally designing ligands for carbohydrate targets; and may be expanded to other clinically relevant gangliosides.

Key words

Saturation transfer difference NMR Transferred NOE Antibody–carbohydrate interactions Peptide–carbohydrate interaction NMR structure calculations Molecular modeling Ganglioside GD2 Peptide mimetics Cancer 


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Wenyong Tong
    • 1
    • 2
  • Tara Sprules
    • 3
  • Kalle Gehring
    • 4
    • 3
  • H. Uri Saragovi
    • 1
    • 5
    Email author
  1. 1.Lady Davis Institute-Jewish General HospitalMontréalCanada
  2. 2.Departments of Pharmacology and Therapeutics, and the Cancer CenterMcGill UniversityMontrealCanada
  3. 3.Quebec/Eastern Canada High Field NMR FacilityMcGill UniversityMontrealCanada
  4. 4.Department of Biochemistry and the Cancer CenterMcGill UniversityMontrealCanada
  5. 5.Departments of Pharmacology and Therapeutics, Oncology and the Cancer CenterMcGill UniversityMontréalCanada

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