J 2012

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 et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.831

RIV identification code

RIV/00216224:14740/12:00061938

Organization unit

Central European Institute of Technology

DOI

UT WoS

000303497600019

Keywords in English

carbohydrates; click chemistry; glycoclusters; lectin; multivalency

Tags

Tags

International impact, Reviewed
Změněno: 6/4/2013 18:15, Olga Křížová

Abstract

V originále

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

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