Rational Design and Synthesis of Optimized Glycoclusters for Multivalent Lectin-Carbohydrate Interactions: Influence of the Linker Arm

CECIONI, Samy, Jean-Pierre PRALY, Susan E MATTHEWS, Michaela WIMMEROVÁ, Anne IMBERTY and Sebastien VIDAL. Rational Design and Synthesis of Optimized Glycoclusters for Multivalent Lectin-Carbohydrate Interactions: Influence of the Linker Arm. Chemistry - A European Journal. WEINHEIM: WILEY-VCH, 2012, vol. 18, No 20, p. 6250-6263. ISSN 0947-6539. Available from: https://dx.doi.org/10.1002/chem.201200010.

Basic information

• Original name: Rational Design and Synthesis of Optimized Glycoclusters for Multivalent Lectin-Carbohydrate Interactions: Influence of the Linker Arm
• Authors: CECIONI, Samy (250 France), Jean-Pierre PRALY (250 France), Susan E MATTHEWS (826 United Kingdom of Great Britain and Northern Ireland), Michaela WIMMEROVÁ (203 Czech Republic, guarantor, belonging to the institution), Anne IMBERTY (250 France) and Sebastien VIDAL (250 France).
• Edition: Chemistry - A European Journal, WEINHEIM, WILEY-VCH, 2012, 0947-6539.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: Germany
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 5.831
• RIV identification code: RIV/00216224:14740/12:00061938
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1002/chem.201200010
• UT WoS: 000303497600019
• Keywords in English: carbohydrates; click chemistry; glycoclusters; lectin; multivalency
• Tags: ok, rivok
• Tags: International impact, Reviewed

Abstract

The design of multivalent glycoclusters requires the conjugation of biologically relevant carbohydrate epitopes functionalized with linker arms to multivalent core scaffolds. The multigram-scale syntheses of three structurally modified triethyleneglycol analogues that incorporate amide moiety(ies) and/or a phenyl ring offer convenient access to a series of carbohydrate probes with different water solubilities and rigidities. Evaluation of flexibility and determination of preferred conformations were performed by conformational analysis. Conjugation of the azido-functionalized carbohydrates with tetra-propargylated core scaffolds afforded a library of 18 tetravalent glycoclusters, in high yields, by CuI-catalyzed azidealkyne cycloaddition (CuAAC). The compounds were evaluated for their ability to bind to PA-IL (the LecA lectin from the opportunistic pathogen Pseudomonas aeruginosa). Biochemical evaluation through inhibition of hemagglutination assays (HIA), enzyme-linked lectin assays (ELLA), surface plasmon resonance (SPR), and isothermal titration microcalorimetry (ITC) revealed improved and unprecedented affinities for one of the monovalent probes (K-d=5.8 mu M) and also for a number of the tetravalent compounds that provide several new nanomolar ligands for this tetrameric lectin.

Links

• ME08008, research and development project: Name: Návrh antibakteriálních a antivirových léků na bázi cukrů a glykomimetik

Investor: Ministry of Education, Youth and Sports of the CR, Design of Carbohydrates and Glycomimetics as Antibacterial and Antiviral Drugs, Research and Development Programme KONTAKT (ME)

• MSM0021622413, plan (intention): Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment

• 205872, interní kód MU: Name: Program developing interdisciplinary research POtential for the STudies of BIOMolecular INteractions (Acronym: POSTBIOMIN)

Investor: European Union, Program developing interdisciplinary research POtential for the STudies of BIOMolecular INteractions, Capacities