Sugar mimics: an artificial receptor for cholera toxin

Anna Bernardi; Anna Checchia; Paola Brocca; Sandro Sonnino; Fabio Zuccotto

doi:10.1021/ja983567c

Sugar mimics: an artificial receptor for cholera toxin

Anna Bernardi
, Anna Checchia
, Paola Brocca
, Sandro Sonnino
, Fabio Zuccotto

Drug Discovery Unit

Research output: Contribution to journal › Article › peer-review

56 Citations (Scopus)

Abstract

The paper describes the pseudosugar 2 [Galβ1-3GalNAcβ1-4(NeuAcα2- 3)DCCHD], a high affinity binder of cholera toxin (CT). The molecule was designed using molecular modeling techniques to mimic the natural CT membrane receptor, ganglioside GM1. The central residue of GM1, a 3,4-disubstituted galactose unit, was recognized as the ganglioside scaffold element and substituted with a conformationally locked cyclohexanediol (DCCHD). DCCHD was synthesized in enantiopure form using enantioselective Diels Alder methodology and regioselectively α-sialylation at the equatorial position. Glycosylation with a Galβ(1-3)-GalNAc donor completed the synthesis of 2. The solution structure of 2 and its binding ability to CT were found to be analogous to those of the GM1 oligosaccharide.

Original language	English
Pages (from-to)	2032-2036
Number of pages	5
Journal	Journal of the American Chemical Society
Volume	121
Issue number	10
Early online date	2 Mar 1999
DOIs	https://doi.org/10.1021/ja983567c
Publication status	Published - 17 Mar 1999

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

General Chemistry

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10.1021/ja983567c

Cite this

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title = "Sugar mimics: an artificial receptor for cholera toxin",

abstract = "The paper describes the pseudosugar 2 [Galβ1-3GalNAcβ1-4(NeuAcα2- 3)DCCHD], a high affinity binder of cholera toxin (CT). The molecule was designed using molecular modeling techniques to mimic the natural CT membrane receptor, ganglioside GM1. The central residue of GM1, a 3,4-disubstituted galactose unit, was recognized as the ganglioside scaffold element and substituted with a conformationally locked cyclohexanediol (DCCHD). DCCHD was synthesized in enantiopure form using enantioselective Diels Alder methodology and regioselectively α-sialylation at the equatorial position. Glycosylation with a Galβ(1-3)-GalNAc donor completed the synthesis of 2. The solution structure of 2 and its binding ability to CT were found to be analogous to those of the GM1 oligosaccharide.",

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T1 - Sugar mimics

T2 - an artificial receptor for cholera toxin

AU - Bernardi, Anna

AU - Checchia, Anna

AU - Brocca, Paola

AU - Sonnino, Sandro

AU - Zuccotto, Fabio

PY - 1999/3/17

Y1 - 1999/3/17

N2 - The paper describes the pseudosugar 2 [Galβ1-3GalNAcβ1-4(NeuAcα2- 3)DCCHD], a high affinity binder of cholera toxin (CT). The molecule was designed using molecular modeling techniques to mimic the natural CT membrane receptor, ganglioside GM1. The central residue of GM1, a 3,4-disubstituted galactose unit, was recognized as the ganglioside scaffold element and substituted with a conformationally locked cyclohexanediol (DCCHD). DCCHD was synthesized in enantiopure form using enantioselective Diels Alder methodology and regioselectively α-sialylation at the equatorial position. Glycosylation with a Galβ(1-3)-GalNAc donor completed the synthesis of 2. The solution structure of 2 and its binding ability to CT were found to be analogous to those of the GM1 oligosaccharide.

AB - The paper describes the pseudosugar 2 [Galβ1-3GalNAcβ1-4(NeuAcα2- 3)DCCHD], a high affinity binder of cholera toxin (CT). The molecule was designed using molecular modeling techniques to mimic the natural CT membrane receptor, ganglioside GM1. The central residue of GM1, a 3,4-disubstituted galactose unit, was recognized as the ganglioside scaffold element and substituted with a conformationally locked cyclohexanediol (DCCHD). DCCHD was synthesized in enantiopure form using enantioselective Diels Alder methodology and regioselectively α-sialylation at the equatorial position. Glycosylation with a Galβ(1-3)-GalNAc donor completed the synthesis of 2. The solution structure of 2 and its binding ability to CT were found to be analogous to those of the GM1 oligosaccharide.

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DO - 10.1021/ja983567c

M3 - Article

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Sugar mimics: an artificial receptor for cholera toxin

Abstract

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ASJC Scopus subject areas

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