Glycotentacles:Synthesis of Cyclic Glycopeptides,Toward a Tailored Blocker of Influenza Virus Hemagglutinin

摘要

influenza virus infection is initiated by the binding of hemagglutinin (HA),a viral carbohydrate-binding membrane protein,to sialic acid-containing oligosaccharides,such as GM3 trisaccharide [Neu5Acalpha(2,3)Galbeta(1,4)Glc],on the host cell surfaces.~[1]Since thismolecular-recognition process leads to the host cell-virus adhesion stage,molecules with a high affinity for the viral HA would be potent candidates for blockers of the influenza virus.Various typest of HA blockers carrying sialooligosaccharides have been synthesized over the last decade.~[2]Enhanced blocking effects by the multidentate (multivalent) glycoligands were often found by clustering~[3] the sialooligosaccharides on macromolecular scaffolds,such as synthetic polymers,~[4] cyclodextrins,~[5]and dendrimers,~[6]although the mechanism of this multiple interaction has not yet been fully investigated.