Aromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factor  

作　　者：Xiaoxuan Yan Chao Chen Chunxi Wang Wenxian Lan Jianguo Wang Chunyang Cao 

机构地区：[1]State Key Laboratory of Bioorganic and Natural Products Chemistry,Shanghai Institute of Organic Chemistry,Center for Excellence in Molecular Synthesis,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China [2]State Key Laboratory of Elemento-organic Chemistry,National Pesticide Engineering Research Center,College of Chemistry,Nankai University,Tianjin 300071,China [3]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第5期725-735,共11页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.21977110,21977057,22174155 and 22177127);the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB 20000000);the Center for Excellence in Molecular Synthesis,CAS(No.FZHCZY020600).

摘　　要：APOBEC3G(A3G)is a member of cytosine deaminase family with a variety of innate immune functions.It displays activities against retrovirus and retrotransposon by inhibition of virus infectivity factor(Vif)-deficient HIV-1 replication.The interaction between A3G N-terminal domain and Vif directs the cellular Cullin 5 E3-ubiquitin ligase complex to ubiquitinate A3G,and leads to A3G proteasomal degradation,which is a potential target for anti-HIV drug.Currently,there are very few reports about stable small molecules targeting the interaction between A3G and Vif.In this study,we screened two series of small molecules containing carbamyl sulfamide bond or disulfide bond as bridges of two different aromatic rings.Five asymmetrical disulfides were successfully identified against interaction between A3G and Vif with the IC_(50)values close to or smaller than 1μM,especially,not through covalently binding with A3G or Vif.They restore the A3G expression in the presence of Vif by inhibiting Vif-induced A3G ubiquitination and degradation.This study opens a way to the discovery of new anti-HIV drugs.

关 键 词：APOBEC3G VIF INTERACTION HIV-1 aromatic disulfide 

分 类 号：O62[理学—有机化学]