title: Design and synthesis of glycoprotein-based multivalent glyco-ligands for influenza hemagglutinin and human galectin-3.
abstract: We report a facile synthesis of glycoprotein-based glyco-ligands and their binding with influenza hemagglutinin and human galectin-3. Human serum albumin (HSA) was used as the scaffold and an Asn-linked complex type N-glycan prepared from chicken eggs was used as the glycan building block. It was found that Cu(I)-catalyzed alkyne-azide cycloaddition reaction (click chemistry) between the alkyne-labeled glycan and the azide-tagged HSA led to an efficient formation of the glycoconjugates. The density of glycan ligands on the protein scaffold was readily varied by changing the molar ratios of the two reactants. Binding studies indicated that the sialylated and desialylated multivalent glycoligands could selectively bind to influenza hemagglutinin and human galectin-3, respectively, with high affinity. In the two glycan-lectin interactions, a clear multivalent effect was observed. Moreover, a cell-based assay showed that the synthetic multivalent glyco-ligands could efficiently inhibit the attachment of galectin-3 to human prostate cancer and lung cancer cell lines. This study suggests that the synthetic glycoprotein-based glyco-ligands can be useful for different applications, including blocking the function of galectin-3 in cancer metastasis.
authors: Institute of Human Virology and Department of Biochemistry & Molecular Biology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA.
authors: Helen
authors: H
authors: Wang
authors: Wei
authors: W
authors: Huang
authors: Jared
authors: J
authors: Orwenyo
authors: Aditi
authors: A
authors: Banerjee
authors: Gerardo R
authors: GR
authors: Vasta
authors: Lai-Xi
authors: LX
authors: Wang
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D002645:Chickens; D057930:Click Chemistry; D015195:Drug Design; D037502:Galectin 3 / Q000378:metabolism*; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006801:Humans; D007251:Influenza, Human / Q000821:virology*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000378:metabolism*; D012709:Serum Albumin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D037502:Galectin 3; D006001:Glycoconjugates; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008024:Ligands; D012709:Serum Albumin