The Specific Extraction Of Fucosylated-glycoproteins And The Synthesis Of Zanamivir Analogs As Neuraminidase Inhibitors

Many diseases and cancers are closely related to low-abundance proteins,such as glycosylated protein.The separation,enrichment and detections and analysis of these low-abundance proteins from the complex biological samples is still a crtical problem.Click chemistry can be reacted in mild environment with high speed and high selectivity.The work in first part of this paper was attempting to magnetic nanoparticles functionalized with disulfide linked alkynyl group reacting with cell surface azido modified fiucosylated glycoproteins expressed by metabolically engineered oligosaccharides,through click reaction.Thus,the fucosylated glycoprotein can be separated magnetically.Firstly,the magnetic functional nanoparticles with cleavable disulfide bonds and alkyne groups,which designed by our group,were detected by fluorescence labeling to verify the function.At the same time,the un-natural 6 azido fucose was expressed on Jurkat cells by oligosaccharide metabolism engineering,then the cell smears were stained with rhodamine to verify the expression.Because the abundance of fucosylated proteins is low,the SDS-PAGE was not enough sensitive to detect the separation.This method could not detect the enrichment of fucosylated proteins from Jurkat cells.Then,the azido-fucose protein was directly released from the alkyne-based magnetic nanoparticles and subjected to LC-MS/MS analysis.In the second part of this paper,aiming at seeking a new Influenza A virus neuraminidase inhibitors.Using sialic acid as the starting material,through glycosylation,selective protection,oxidation,and reduction and etc.to synthesis the analogues of zanamivir.Carrying out the design and synthesis of zanamivir analogues.Hopes cloud find a new type of zanamivir analogues to treat flu.