Synthesis of Multivalent Carbohydrate-Centered Glycoclusters as Nanomolar Ligands of the Bacterial Lectin LecA from Pseudomonas aeruginosa

被引：53

作者：

Gening, Marina L. ^{[1
]}

Titov, Denis V. ^{[1
]}

Cecioni, Samy ^{[2
,3
]}

Audfray, Aymeric ^{[2
]}

Gerbst, Alexey G. ^{[1
]}

Tsvetkov, Yury E. ^{[1
]}

Krylov, Vadim B. ^{[1
]}

Imberty, Anne ^{[2
]}

Nifantiev, Nikolay E. ^{[1
]}

Vidal, Sebastien ^{[3
]}

机构：

[1] Russian Acad Sci, ND Zelinsky Inst Organ Chem, Lab Glycoconjugate Chem, Moscow 119991, Russia

[2] Grenoble Univ & ICMG, Ctr Rech Macromol Vegetales CERMAV CNRS UPR 5301, F-38041 Grenoble, France

[3] Univ Lyon 1, Inst Chim & Biochim Mol & Supramol, Lab Chim Organ Glycochim 2, CNRS,UMR 5246, F-69622 Villeurbanne, France

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2013年 / 19卷 / 28期

关键词：

click chemistry; glucosamines; glycocluster; lectins; Pseudomonas aeruginosa; oligosaccharides; HIGH-AFFINITY; STRUCTURAL BASIS; PA-IL; RECOGNITION; BINDING; DESIGN; PLANT;

D O I：

10.1002/chem.201300135

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A family of fifteen glycoclusters based on a cyclic oligo-(16)--D-glucosamine core has been designed as potential inhibitors of the bacterial lectin LecA with various valencies (from 2 to 4) and linkers. Evaluation of their binding properties towards LecA has been performed by a combination of hemagglutination inhibition assays (HIA), enzyme-linked lectin assays (ELLA), and isothermal titration microcalorimetry (ITC). Divalent ligands displayed dissociation constants in the sub-micromolar range and tetravalent ligands displayed low nanomolar affinities for this lectin. The influence of the linker could also be demonstrated; aromatic moieties are the best scaffolds for binding to the lectin. The affinities observed in vitro were then correlated with molecular models to rationalize the possible binding modes of these glycoclusters with the bacterial lectin.

引用

页码：9272 / 9285

页数：14

共 50 条

[1]

[Anonymous], 2011, ANGEW CHEM INT ED, V50, P10631

[2]

[Anonymous], 1998, ANGEW CHEM INT ED, V37, P2754

[3]

[Anonymous], 2009, ANGEW CHEM INT ED, V48, P2576

[4] The Protein Data Bank [J].

Berman, HM ;

Westbrook, J ;

Feng, Z ;

Gilliland, G ;

Bhat, TN ;

Weissig, H ;

Shindyalov, IN ;

Bourne, PE .

NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242

[5] Structural Basis of the Preferential Binding for Globo-Series Glycosphingolipids Displayed by Pseudomonas aeruginosa Lectin I [J].

Blanchard, Bertrand ;

Nurisso, Alessandra ;

Hollville, Emilie ;

Tetaud, Cecile ;

Wiels, Joelle ;

Pokorna, Martina ;

Wimmerova, Michaela ;

Varrot, Annabelle ;

Imberty, Anne .

JOURNAL OF MOLECULAR BIOLOGY, 2008, 383 (04) :837-853

[6]

Boturyn D., 2009, ANGEW CHEM, V121, P2614

[7]

Cecioni S, 2012, CARBOHYD CHEM, V1, P175

[8] Synthesis of lactosylated glycoclusters and inhibition studies with plant and human lectins [J].

Cecioni, Samy ;

Matthews, Susan E. ;

Blanchard, Helen ;

Praly, Jean-Pierre ;

Imberty, Anne ;

Vidal, Sebastien .

CARBOHYDRATE RESEARCH, 2012, 356 :132-141

[9] Rational Design and Synthesis of Optimized Glycoclusters for Multivalent Lectin-Carbohydrate Interactions: Influence of the Linker Arm [J].

Cecioni, Samy ;

Praly, Jean-Pierre ;

Matthews, Susan E. ;

Wimmerova, Michaela ;

Imberty, Anne ;

Vidal, Sebastien .

CHEMISTRY-A EUROPEAN JOURNAL, 2012, 18 (20) :6250-6263

[10] Synthesis of Dodecavalent Fullerene-Based Glycoclusters and Evaluation of Their Binding Properties towards a Bacterial Lectin [J].

Cecioni, Samy ;

Oerthel, Vincent ;

Iehl, Julien ;

Holler, Michel ;

Goyard, David ;

Praly, Jean-Pierre ;

Imberty, Anne ;

Nierengarten, Jean-Francois ;

Vidal, Sebastien .

CHEMISTRY-A EUROPEAN JOURNAL, 2011, 17 (11) :3252-3261

← 1 2 3 4 5 →