Aromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factor
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...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2022-05-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022049 |
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| author | Yan Xiaoxuan Chen Chao Wang Chunxi Lan Wenxian Wang Jianguo Cao Chunyang |
| author_facet | Yan Xiaoxuan Chen Chao Wang Chunxi Lan Wenxian Wang Jianguo Cao Chunyang |
| author_sort | Yan Xiaoxuan |
| collection | DOAJ |
| description | 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<sub>50</sub> values close to or smaller than <sc>1 μM,</sc> 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. |
| format | Article |
| id | doaj-art-87fd81fa6b71400bb1ef0d8d61fff8cb |
| institution | DOAJ |
| issn | 1672-9145 |
| language | English |
| publishDate | 2022-05-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-87fd81fa6b71400bb1ef0d8d61fff8cb2025-08-20T03:07:05ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-05-015472573510.3724/abbs.202204920d259ccAromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factorYan Xiaoxuan0Chen Chao1Wang Chunxi2Lan Wenxian3Wang Jianguo4Cao Chunyang5["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","University of Chinese Academy of Sciences, Beijing 100049, China"]["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"]["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"]["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"]["State Key Laboratory of Elemento-organic Chemistry, National Pesticide Engineering Research Center, College of Chemistry, Nankai University, Tianjin 300071, China"]["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","University of Chinese Academy of Sciences, Beijing 100049, China"]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<sub>50</sub> values close to or smaller than <sc>1 μM,</sc> 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.https://www.sciengine.com/doi/10.3724/abbs.2022049APOBEC3GVifinteractionHIV-1aromatic disulfide |
| spellingShingle | Yan Xiaoxuan Chen Chao Wang Chunxi Lan Wenxian Wang Jianguo Cao Chunyang Aromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factor Acta Biochimica et Biophysica Sinica APOBEC3G Vif interaction HIV-1 aromatic disulfide |
| title | Aromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factor |
| title_full | Aromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factor |
| title_fullStr | Aromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factor |
| title_full_unstemmed | Aromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factor |
| title_short | Aromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factor |
| title_sort | aromatic disulfides as potential inhibitors against interaction between deaminase apobec3g and hiv infectivity factor |
| topic | APOBEC3G Vif interaction HIV-1 aromatic disulfide |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022049 |
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