Heterocyclic Molecules Tethered Branched Polymers with Innate Immune Stimulating Activity  

作　　者：Jiayu Zhao Liping Liu Yibo Wang Zichao Huang Yu Zhang Ruirui Qiao Thomas P.Davis Zhaohui Tang Wantong Song Xuesi Chen 

机构地区：[1]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022 [2]School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei 230026 [3]Laboratory of Chemical Biology,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022 [4]Jilin Biomedical Polymers Engineering Laboratory,Changchun 130022 [5]Australian Institute of Bioengineering and Nanotechnology,The University of Queensland,Brisbane,Queensland 4072

出　　处：《CCS Chemistry》2024年第5期1278-1288,共11页中国化学会会刊（英文）

基　　金：the Bureau of International Cooperation Chinese Academy of Sciences(grant no.121522KYSB20200029);National Natural Science Foundation of China(grant nos.22222509,52025035,52003268,and 51973215);Jilin Province Science and Technology Development Plan(grant nos.YDZJ202101-ZYTS131 and 20220402037GH);Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(grant no.20210504001GH);Changchun Science and Technology Development Plan(grant no.21ZY09);the Youth Innovation Promotion Association of Chinese Academy of Sciences(grant no.2020232).

摘　　要：We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecules to branched polyethylenimine(bPEI),over 70%of them could induce the secretion of interferon-β(IFN-β)from murine dendritic and human leukemia monocytic(DC2.4 and THP-1)cells through activating the stimulator of interferon genes(STING)pathway.We further proved that this kind of innate stimulating activity was dependent on the macromolecular architecture as heterocyclic molecules tethered linear PEI(lPEI)or dendritic polyamidoamine(PAMAM)induced no or much less IFN-βsecretion.Furthermore,we prepared a series of poly-L-lysine(PLL)-derivatives with different branches to tether with heterocyclic molecules and proved that this kind of bPEI-like structure was important in en hancing the binding affinity with STING proteins and for exhibiting innate stimulating activity.

关 键 词：bioactive materials POLYMERS HETEROCYCLES branched structure IMMUNITY 

分 类 号：O62[理学—有机化学]