Journal of the Chemical Society Perkin Transactions 1 · 2001 · 11 citations · 11 references
PharmacyInfectious DiseasesMedicinal ChemistryEnzymologyMolecular VirologyVirologyAntibody ConjugatesAntibody ConjugationAntibody-drug ConjugatesAntiviral AgentsEnzyme InhibitionGlycoengineering Of AntibodiesAmide LinkersAntibody-mediated Viral NeutralizationAntibody-mediated Virus NeutralizationEnzymatic GlycosylationGlycan Binding AffinityInhibitor Binding AffinityRhinovirus InfectionViral Protein Glycosylation
The syntheses of αGal-conjugated anti-rhinovirus agents 1, 2 and 3 and their abilities to inhibit αGal binding of human anti-Gal antibody are described. An efficient enzymatic glycosylation using a novel fusion protein serves to provide the key αGal intermediate 7, which is elaborated to αGal amines 9, 12 and 14 with various tethers. The conjugates are then formed by amide coupling of these amines to heterocyclic acid 18 in the presence of 1,1′-carbonyldiimidazole (CDI), followed by deprotection of the αGal part. Conjugate 3 having a triethylene glycol linker displays the highest binding affinity to human anti-Gal antibody as tested by ELISA.
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