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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Nature communications
2024
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39738095/ |
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| _version_ | 1868266263022665728 |
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| author | Li, Tian Jiang, Shan Dai, Yuanhao Wu, Xia Guo, Huihui Shi, Liang Sang, Xueli Ren, Li Wang, Jie Shi, Lili Zhou, Wenming Li, Houhua Hao, Hong-Dong |
| author_facet | Li, Tian Jiang, Shan Dai, Yuanhao Wu, Xia Guo, Huihui Shi, Liang Sang, Xueli Ren, Li Wang, Jie Shi, Lili Zhou, Wenming Li, Houhua Hao, Hong-Dong Li, Tian Jiang, Shan Dai, Yuanhao Wu, Xia Guo, Huihui Shi, Liang Sang, Xueli Ren, Li Wang, Jie Shi, Lili Zhou, Wenming Li, Houhua Hao, Hong-Dong |
| collection | PubMed - marine biology |
| contents | Total synthesis and target identification of marine cyclopiane diterpenes. Li, Tian Jiang, Shan Dai, Yuanhao Wu, Xia Guo, Huihui Shi, Liang Sang, Xueli Ren, Li Wang, Jie Shi, Lili Zhou, Wenming Li, Houhua Hao, Hong-Dong Diterpenes Animals Mice Cyclization RAW 264.7 Cells Autophagy Humans Mitochondria Anti-Inflammatory Agents Cyclopentanes Proteomics Macrophages Aquatic Organisms Marine cyclopianes are a family of diterpenoid with novel carbon skeleton and diverse biological activities. Herein, we report our synthetic and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 (IRGM1) as a cellular target. Our asymmetric synthesis commences from Wieland-Miescher ketone and features a sequential intramolecular Pauson-Khand reaction and gold-catalyzed Nazarov cyclization to rapidly construct the 6-5-5-5 tetracyclic skeleton. The stereocontrolled cyclopentenone construction is further investigated on complex settings to demonstrate its synthetic utility. Furthermore, using an alkyne-tagged conidiogenone C-derived probe, IRGM1, a master regulator of type I interferon responses, is identified as a key cellular target of conidiogenone C responsible for its anti-inflammatory activity. Preliminary mechanism of action studies shows that conidiogenone C activates IRGM1-mediate dysfunctional mitochondria autophagy to maintain mitochondria quality control of inflammatory macrophages. |
| format | Artículo científico |
| id | pubmed_39738095 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | Nature communications |
| record_format | pubmed |
| spellingShingle | Total synthesis and target identification of marine cyclopiane diterpenes. Li, Tian Jiang, Shan Dai, Yuanhao Wu, Xia Guo, Huihui Shi, Liang Sang, Xueli Ren, Li Wang, Jie Shi, Lili Zhou, Wenming Li, Houhua Hao, Hong-Dong Diterpenes Animals Mice Cyclization RAW 264.7 Cells Autophagy Humans Mitochondria Anti-Inflammatory Agents Cyclopentanes Proteomics Macrophages Aquatic Organisms Total synthesis and target identification of marine cyclopiane diterpenes. Li, Tian Jiang, Shan Dai, Yuanhao Wu, Xia Guo, Huihui Shi, Liang Sang, Xueli Ren, Li Wang, Jie Shi, Lili Zhou, Wenming Li, Houhua Hao, Hong-Dong Diterpenes Animals Mice Cyclization RAW 264.7 Cells Autophagy Humans Mitochondria Anti-Inflammatory Agents Cyclopentanes Proteomics Macrophages Aquatic Organisms Marine cyclopianes are a family of diterpenoid with novel carbon skeleton and diverse biological activities. Herein, we report our synthetic and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 (IRGM1) as a cellular target. Our asymmetric synthesis commences from Wieland-Miescher ketone and features a sequential intramolecular Pauson-Khand reaction and gold-catalyzed Nazarov cyclization to rapidly construct the 6-5-5-5 tetracyclic skeleton. The stereocontrolled cyclopentenone construction is further investigated on complex settings to demonstrate its synthetic utility. Furthermore, using an alkyne-tagged conidiogenone C-derived probe, IRGM1, a master regulator of type I interferon responses, is identified as a key cellular target of conidiogenone C responsible for its anti-inflammatory activity. Preliminary mechanism of action studies shows that conidiogenone C activates IRGM1-mediate dysfunctional mitochondria autophagy to maintain mitochondria quality control of inflammatory macrophages. |
| title | Total synthesis and target identification of marine cyclopiane diterpenes. |
| topic | Diterpenes Animals Mice Cyclization RAW 264.7 Cells Autophagy Humans Mitochondria Anti-Inflammatory Agents Cyclopentanes Proteomics Macrophages Aquatic Organisms |
| url | https://pubmed.ncbi.nlm.nih.gov/39738095/ |