title: CuAAC synthesis of resorcin[4]arene-based glycoclusters as multivalent ligands of lectins.
abstract: 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.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich, UK NR4 7TJ.
authors.forename: Zahid H
authors.initials: ZH
authors.lastname: Soomro
authors.forename: Samy
authors.initials: S
authors.lastname: Cecioni
authors.forename: Helen
authors.initials: H
authors.lastname: Blanchard
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Praly
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vidal
authors.forename: Susan E
authors.initials: SE
authors.lastname: Matthews
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D047250:Calixarenes / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005690:Galactose / Q000138:chemical synthesis* / Q000737:chemistry; D037483:Galectin 1 / Q000037:antagonists & inhibitors; D006801:Humans; D007785:Lactose / Q000138:chemical synthesis* / Q000737:chemistry; D037102:Lectins / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D001386:Azides; D037483:Galectin 1; D037102:Lectins; D008024:Ligands; C466160:resorcinarene; D047250:Calixarenes; D010649:Phenylalanine; D003300:Copper; D007785:Lactose; D005690:Galactose