Ganglioside GM1 mimics: Lipophilic substituents improve affinity for cholera toxin

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 21, 2003, Pages 3831-3834

  Arosio, Daniela ^a   Baretti, Sergio ^a   Cattaldo, Stefania ^a   Potenza, Donatella ^a   Bernardi, Anna ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 HYDROXY 3 CYCLOHEXYLPROPIONIC ACID; 2 HYDROXY 3 PHENYLPROPIONIC ACID; CHOLERA TOXIN; GANGLIOSIDE GM1; LACTIC ACID; LIGAND; PROPIONIC ACID DERIVATIVE; SIALIC ACID; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; ENANTIOMER; LIPOPHILICITY; NUCLEAR MAGNETIC RESONANCE; NUCLEAR OVERHAUSER EFFECT;

EID: 0141545065     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.07.007     Document Type: Article

References (23)

1. Sears P., Wong C.H. Angew. Chem. 111:1999;2446. Sears, P.; Wong, C. H. Angew. Chem. Int. Ed. 1999, 38, 2300, and references therein.
2. For a review, see: Bernardi A., Arosio D., Sonnino S. Neurochem. Res. 27:2002;539.
3. Bernardi A., Checchia A., Brocca P., Sonnino S., Zuccotto F. J. Am. Chem. Soc. 121:1999;2032.
4. Bernardi A., Boschin G., Checchia A., Lattanzio M., Manzoni L., Potenza D., Scolastico C. Eur. J. Org. Chem. 6:1999;1311.
5. Bernardi A., Carrettoni L., Grosso Ciponte A., Monti D., Sonnino S. Bioorg. Med. Chem. Lett. 10:2000;2197.
6. For a previous report on the use of hydroxyacids to mimic sialic acid in the context of sialyl-LewisX, see: Kolb H.C., Ernst B. Chem. Eur. J. 3:1997;1571. In this case, a (S)-hydroxyacid was found to be the best replacement for NeuAc.
7. Bernardi A., Potenza D., Capelli A.M., Garcìa-Herrero A., Cañada F.J., Jiménez-Barbero J. Chem. Eur. J. 8:2002;4597.
8. Merritt E.A., Sarfaty S., Jobling M.G., Chang T., Holmes R.K., Hirst T.R., Hol W.G. J. Protein Sci. 6:1997;1516.
9. Schön A., Freire E. Biochem. 28:1989;5019.
10. Bernardi A., Arosio D., Manzoni L., Micheli F., Pasquarello A., Seneci P. J. Org. Chem. 66:2001;6209.
11. David S., Hanessian S. Tetrahedron. 41:1985;643.
12. 2O, 400 MHz): 22.8; 26.1; 26.2; 27.5; 28.4; 33.0; 33.4; 34.0; 40.4; 40.6; 44.7; 52.1; 61.2; 68.6; 69.2; 71.0; 72.5; 72.6; 72.7; 75.3; 78.4; 79.6; 80.4; 101.4; 105.5.
13. Mertz J.A., McCann J.A., Picking W.D. Biochem. Biophys. Res. Commun. 226:1996;140.
14. 3, pH 7.5. Fluorescence measurements were made at room temperature with a Perkin-Elmer LS-50 spectrofluorometer. The excitation wavelength was 280 nm, and the spectrum was recorded between 300 and 450 nm.
15. Hwang T.L., Shaka A.J. J. Am. Chem. Soc. 114:1992;3157 Hwang T.L., Shaka A.J. J. Magn. Res. Ser. B. 102:1993;155.
16. Hwang T.L., Shaka A.J. J. Am. Chem. Soc. 114:1992;3157 Hwang T.L., Shaka A.J. J. Magn. Res. Ser. B. 102:1993;155.
17. No analogous crosspeaks were detected between the GalNAc α protons and the cyclohexyl ring in 3.
18. A conformational search was performed using the MC/EM protocol of Macromodel 7.0, the AMBER* force field, and the GB/SA water solvation model, as described in ref 7. The parameters developed by Kolb and Ernst (from ref 6) were used for the hydroxyacid fragment. For a description of Macromodel, see: Mohamadi F., Richards N.G.J., Guida W.C., Liskamp R., Lipton M., Caufield C., Chang G., Hendrickson T., Still W.C. J. Comp. Chem. 11:1990;440.
19. (a) Weis W.I., Drickamer K. Annu. Rev. Biochem. 65:1996;441
20. (b) Elgavish S., Shaanan B. J. Mol. Biol. 277:1998;917
21. (c) Quiocho F.A. Annu. Rev. Biochem. 55:1986;287
22. (d) Vyas N.K. Curr. Opin. Struct. Biol. 1:1991;732
23. (e) Quiocho F.A. Biochem. Soc. Trans. 21:1993;442.