Intramolecular carbohydrate-aromatic interactions and intermolecular van der Waals interactions enhance the molecular recognition ability of GM1 glycomimetics for cholera toxin

Chemistry : a European Journal
Anna BernardiJesús Jiménez-Barbero

Abstract

The design and synthesis of two GM1 glycomimetics, 6 and 7, and analysis of their conformation in the free state and when complexed to cholera toxin is described. These compounds, which include an (R)-cyclohexyllactic acid and an (R)-phenyllactic acid fragment, respectively, display significant affinity for cholera toxin. A detailed NMR spectroscopy study of the toxin/glycomimetic complexes, assisted by molecular modeling techniques, has allowed their interactions with the toxin to be explained at the atomic level. It is shown that intramolecular van der Waals and CH-pi carbohydrate-aromatic interactions define the conformational properties of 7, which adopts a three-dimensional structure significantly preorganized for proper interaction with the toxin. The exploitation of this kind of sugar-aromatic interaction, which is very well described in the context of carbohydrate/protein complexes, may open new avenues for the rational design of sugar mimics.

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Citations

Sep 29, 2011·European Biophysics Journal : EBJ·Jesus Angulo, Pedro M Nieto
Jun 29, 2007·Carbohydrate Research·Crtomir PodlipnikAnna Bernardi
Oct 2, 2007·Journal of the American Chemical Society·M Jack Borrok, Laura L Kiessling
Oct 11, 2008·Journal of the American Chemical Society·Zachary R LaughreyMarcey L Waters
Jan 12, 2013·Current Protein & Peptide Science·Maria del Carmen Fernández-AlonsoJesús Jiménez-Barbero
Apr 5, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·João M C TeixeiraCarlos F G C Geraldes
Feb 6, 2010·Medicinal Research Reviews·Ashish A KulkarniSuri S Iyer
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Dec 23, 2014·Future Medicinal Chemistry·Michelle P ChristiePavla Simerská
Oct 1, 2016·European Journal of Medicinal Chemistry·Vivek AsatiSanjay Kumar Bharti
Jul 12, 2007·Chembiochem : a European Journal of Chemical Biology·Cristina AiroldiFrancesco Peri
Jul 26, 2008·Chembiochem : a European Journal of Chemical Biology·Gabriele TimpanoAnna Bernardi
Mar 26, 2020·Chemistry : a European Journal·Josef HouserJaroslav Koča
Apr 19, 2011·Chembiochem : a European Journal of Chemical Biology·Virginia RoldósJesús Jiménez-Barbero
Oct 11, 2011·Organic & Biomolecular Chemistry·Cinzia GuzziPedro M Nieto
Dec 17, 2009·Current Protocols in Nucleic Acid Chemistry·Gwladys PourceauFrançois Morvan
May 22, 2013·Organic & Biomolecular Chemistry·Jaime Garcia-HartjesHan Zuilhof
Jan 5, 2008·The Journal of Organic Chemistry·Lorena Bautista-IbañezGabriel Cuevas
Jan 7, 2009·The Journal of Organic Chemistry·Gwladys PourceauFrançois Morvan
Feb 21, 2007·Journal of the American Chemical Society·Giancarlo TerraneoAnna Bernardi
Jun 19, 2012·Accounts of Chemical Research·Juan Luis AsensioJesús Jiménez-Barbero
Jun 30, 2005·Journal of the American Chemical Society·Jason N MartinCristina Vicent
Oct 8, 2021·ACS Chemical Biology·Laura L Kiessling, Roger C Diehl
Oct 7, 2021·ChemMedChem·Benedetta GirardiMarko Anderluh

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