Synthesis Of 6-deoxy-N-glycan Polymers And Their Effects On The Function Of Macrophages

A large number of studies have shown that polysaccharides of natural origin have a variety of biological functions,including anti-tumor,anti-virus and immunoregulatory effect,among which the immunomodulatory function has been widely concerned.However,it is difficult to obtain pure polysaccharides from natural sources.Synthetic glycopolymers are mimics in structure to natural polysaccharides.Their properties such as"Multivalent Interaction"and"Cluster Glycoside Effects"enable glycopolymer to mimic natural polysaccharide-mediated biomacromolecular interactions and can be used to study the biological function of polysaccharides.Based on our previous studies,a serial of?(11)?-bifunctional 6-deoxy-N-glycan polymers were synthesized by cyanoxyl-mediated free-radical copolymerization(CMFRP)in one pot.The effects of these synthesized glycopolymers on the function of macrophages were evaluated.The contents in this study is as follows:(1)synthesizing the four 6-deoxy sugars from D-galactose,D-glucose,2-deoxy-2-N-acetylamino-D-glucose,and D-mannose;(2)preparing 6-deoxy-1-N-acryloyl sugar amine from the four 6-deoxy sugars(namely 6-deoxy-D-galactose,6-deoxy-D-glucose,2,6-dideoxy-2-N-acetylamino-D-glucose,and 6-deoxy-D-mannose)and two naturally derived 6-deoxy sugar(L-rhamnose and L-fucose);(3)?(11)?-bifunctional 6-deoxy-N-glycan polymers preparation with 4-azideaniline hydrochloride as a free radical initiator.The structure and average molecular weight of these 6-deoxy-N-glycan polymers were characterized by ~1H-NMR and FT-IR spectra.In addition,the cytotoxicity of these synthesized glycopolymers toward RAW264.7 macrophages was first investigated.Then,the effects of these glycopolymers on the release of cytokines including NO,IL-6 and IL-10 in macrophages were examined.Also,the inhibitory effects of these glycopolymers on the LPS-induced release of macrophages cytokines such as NO,IL-6 and IL-10 were investigated.Results showed that all the synthesized glycopolymers showed no cytotoxicity toward RAW264.7 macrophages at a concentration of 0.5mg/mL.Meanwhile,treatment alone of these synthesized glycopolymers didn't activate the function of macrophages since they have no effect on the release of cytokines such as NO,IL-6and IL-10.However,we found that these glycopolymers could inhibit the release of NO,IL-6and IL-10 cytokines induced by LPS in RAW264.7 macrophages.This indicated that they could exhibit anti-inflammatory effects.Overall,it is the first time to synthesize the 6-deoxy-N-glycan polymers,further enriching the structure types of N-glycopolymers.In addition,the effects of these synthesized glycopolymers on the function of macrophages were also assayed,which showed that they could be developed as new immunomodulating agents.