Glycosidase Inhibition with Fullerene Iminosugar Balls: A Dramatic Multivalent Effect

Compain, Philippe; Decroocq, Camille; Iehl, Julien; Holler, Michel; Hazelard, Damien; Barragán, Teresa Mena; Mellet, Carmen Ortiz; Nierengarten, Jean‐François

doi:10.1002/ange.201002802

Cited by 69 publications

(70 citation statements)

References 40 publications

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“…The reaction has been successfully applied to deactivated substrates bearing up to three electron-withdrawing groups. [29] Experimental Section General Information: THF was dried by passage through an activated alumina column under an atmosphere of argon. [28] The α-selectivity observed may be rationalized in part by preferential nucleophilic attack along axial trajectories on the most favoured or reactive half-chair of the glycosyl cation intermediate according to Woerpel's model.…”

Section: Discussionmentioning

confidence: 99%

Stereoselective Synthesis of α‐Glycosyl Azides by TMSOTf‐Mediated Ring Opening of 1,6‐Anhydro Sugars

2013

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Access to α‐glycosyl azides in modest to high diastereoselectivity by way of TMSN3 ring‐opening of 1,6‐anhydro sugars mediated by TMSOTf is reported. The reaction tolerates a wide variety of functional groups including alcohol, alkyne, azide and ester groups. The efficient synthesis of a pseudopentasaccharide in five steps from commercially available levoglucosan by way of a “click‐click” approach is presented to highlight the interest of the TMSN3 ring‐opening reaction.

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Section: Discussionmentioning

confidence: 99%

Stereoselective Synthesis of α‐Glycosyl Azides by TMSOTf‐Mediated Ring Opening of 1,6‐Anhydro Sugars

2013

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“…[65] Later on, a fullerenebased, dodecavalent deoxynojirimycin cluster was found to be a stronger and selective inhibitor of glycosidases, many times more active than the monovalent deoxynojirimycin derivative used as the reference compound. [66] Based on the results of these initial studies, researchers have also used calixarene platform for the synthesis of iminosugar clusters. [67][68][69] For example, calixarene-iminosugar derivatives 7a and 7b having four 1-deoxynojirimycin units at lower rim of calix [4] arenes (Scheme 3) have been synthesized through coppercatalyzed azide-alkyne cycloaddition (CuAAC) in excellent yields for evaluation of their inhibitory potential against…”

Section: Lower-rim-functionalized Calix[4] Arenesmentioning

confidence: 99%

Functionalized calix[4]arenes as potential therapeutic agents

2017

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Calixarenes, composed of phenolic units linked by methylene bridges at the 2,6-positions, represent a versatile class of macrocyclic compounds in supramolecular chemistry that can host small molecules or ions in their well-defined hydrophobic cavities. In recent years, it has been recognized that this class of compounds has the potential to serve as platform for the design of biological active compounds. Therefore, the calixarenes functionalized with different pharmacophoric groups have been synthesized as target structure by many researchers and were further evaluated for their biological activities. Owing to their promising biological activities such as antiviral, antibacterial, antifungal, and anticancer, the functionalized calixarenes are recently receiving increased attention from pharmaceutical/medicinal chemistry community. In this review, we summarize and discuss the synthetic approaches and the biological potential of functionalized calixarenes, mainly focusing on the selected recent studies for a comprehensive and target-oriented information, which could help in the design and synthesis of new therapeutic agents leading to the development of clinically viable drugs based on these macrocyles. K E Y W O R D Sbiological activity, calixarenes, cone conformation, functionalization, upper/lower rim/annulus

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“…As a recent example, surprising effects have been evidenced for the inhibition of carbohydrate-processing enzymes. [41] The inhibition profile of a fullerene hexakis-adduct decorated with 12 iminosugar residues has been systematically evaluated towards various glycosidases and dramatic multivalent effects have been evidenced, thus opening new avenues for drug discovery. Fullerene hexakis-adducts bearing 12 peripheral mannose moieties have been assayed by using several techniques as inhibitors of FimH, a bacterial adhesin.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Dodecavalent Fullerene‐Based Glycoclusters and Evaluation of Their Binding Properties towards a Bacterial Lectin

Cecioni

Oerthel

Iehl

et al. 2011

Chemistry A European J

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Multivalency is playing a major role in biological processes and particularly in lectin-carbohydrate interactions. The design of high-affinity ligands of lectins should provide molecules capable of interfering with these biological processes and potentially inhibit bacterial or viral infections. Azide-alkyne "click" chemistry was applied to the synthesis of dodecavalent fullerene-based glycoclusters. The conjugation could be efficiently performed from alkyne or azide functions on either partners (i.e. hexakis-fullerene adduct or glycoside). PA-IL is a bacterial lectin from the opportunistic pathogen Pseudomonas aeruginosa and is involved in the recognition of glycoconjugates on human tissues. The glycoclusters obtained were evaluated as ligands of PA-IL and for their potential for competing with its binding to glycosylated surfaces. The affinities measured by hemagglutination inhibition assay (HIA), enzyme-linked lectin assay (ELLA), and surface plasmon resonance (SPR) displayed a significant "glycoside cluster effect" with up to a 12,000-fold increase in binding when comparing a monovalent carbohydrate reference probe with a dodecavalent fullerene-based glycocluster, albeit with some differences depending on the analytical technique.

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Glycosidase Inhibition with Fullerene Iminosugar Balls: A Dramatic Multivalent Effect

Cited by 69 publications

References 40 publications

Stereoselective Synthesis of α‐Glycosyl Azides by TMSOTf‐Mediated Ring Opening of 1,6‐Anhydro Sugars

Stereoselective Synthesis of α‐Glycosyl Azides by TMSOTf‐Mediated Ring Opening of 1,6‐Anhydro Sugars

Functionalized calix[4]arenes as potential therapeutic agents

Synthesis of Dodecavalent Fullerene‐Based Glycoclusters and Evaluation of Their Binding Properties towards a Bacterial Lectin

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