CuAAC synthesis of resorcin[4]arene-based glycoclusters as multivalent ligands of lectins

• Published in: Organic & biomolecular chemistry 2011-10, Vol.9 (19), p.6587-6597
• Main Authors: Soomro, Zahid H, Cecioni, Samy, Blanchard, Helen, Praly, Jean-Pierre, Imberty, Anne, Vidal, Sébastien, Matthews, Susan E
• Format: Article
• Language: English
• Subjects: Alkynes - chemistry; Azides - chemistry; Calixarenes - chemical synthesis; Calixarenes - chemistry; Catalysis; Chemical Sciences; Chemistry Techniques, Synthetic; Click Chemistry; Copper - chemistry; Crystallography, X-Ray; Galactose - chemical synthesis; Galactose - chemistry; Galectin 1 - antagonists & inhibitors; Humans; Lactose - chemical synthesis; Lactose - chemistry; Lectins - chemistry; Lectins - pharmacology; Ligands; Models, Molecular; Molecular Structure; Organic chemistry; Phenylalanine - analogs & derivatives; Phenylalanine - chemical synthesis; Phenylalanine - chemistry; Pseudomonas aeruginosa - chemistry; Stereoisomerism; Structure-Activity Relationship
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c1ob05676j

Synthetic multivalent glycoclusters show promise as anti-adhesives for the treatment of bacterial infections. Here we report the synthesis of a family of tetravalent galactose and lactose functionalised macrocycles based on the resorcin[4]arene core. The development of diastereoselective synthetic routes for the formation of lower-rim propargylated resorcin[4]arenes and their functionalistion via Cu-catalyzed azide-alkyne click chemistry is described. ELLA binding studies confirm that galactose sugar clusters are effective ligands for the PA-IL bacterial lectin of Pseudomonas aeruginosa while poor binding for the lactose-based monovalent probe and no binding could be measured for the multivalent glycoclusters was observed for the human galectin-1.