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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
International journal of molecular sciences
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41155448/ |
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| _version_ | 1868266136423890944 |
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| author | Gao, Jinai Yang, Di Wang, Wanting Huang, Xiaoshan Guo, Ruiyin Cao, Kaixun Lu, Qiumin Wang, Ziyi Lai, Ren Li, Juan |
| author_facet | Gao, Jinai Yang, Di Wang, Wanting Huang, Xiaoshan Guo, Ruiyin Cao, Kaixun Lu, Qiumin Wang, Ziyi Lai, Ren Li, Juan Gao, Jinai Yang, Di Wang, Wanting Huang, Xiaoshan Guo, Ruiyin Cao, Kaixun Lu, Qiumin Wang, Ziyi Lai, Ren Li, Juan |
| collection | PubMed - marine biology |
| contents | Discovery of a Novel Anticoagulant Cystine Knot Peptide from Spider Venom Gland Transcriptome. Gao, Jinai Yang, Di Wang, Wanting Huang, Xiaoshan Guo, Ruiyin Cao, Kaixun Lu, Qiumin Wang, Ziyi Lai, Ren Li, Juan Animals Spider Venoms Anticoagulants Transcriptome Mice Humans Peptides Thrombosis Blood Coagulation Male Cystine Knot Motifs The development of effective anticoagulants remains a critical need in modern medicine, particularly for preventing and treating thromboembolic disorders, such as arterial thrombosis and deep vein thrombosis (DVT), as well as complications like ischemic stroke. This study identifies a cysteine-knotted peptide GC38 (sequence: GCSGKGARCAPSKCCSGLSCGRHGGNMYKSCEWNWKTG) derived from the venom gland transcriptome of the sp. spider, which exerts thrombus-inhibitory effects by potentiating activated protein C (APC) activity. In vitro assays reveal that GC38 enhances APC activity, prolongs plasma clotting time, and shows no significant cytotoxicity or hemolytic activity. Mechanistically, GC38 interacts allosterically with APC; biolayer interferometry (BLI) confirms this direct interaction, with a dissociation constant of 6.16 μM. Additionally, three in vivo thrombosis models (FeCl-induced arterial occlusion, stasis-induced DVT, and cortical photothrombotic stroke) consistently demonstrated that GC38 was effective in alleviating thrombus formation, with tail-bleeding assays confirming its low hemorrhagic risk. Collectively, our findings position GC38 as a pioneering spider venom-derived lead molecule that addresses dual arterial and venous antithrombotic actions. This opens new avenues for developing spider venom-derived peptides as therapeutic agents targeting intravascular coagulation in arteries and veins. |
| format | Artículo científico |
| id | pubmed_41155448 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | International journal of molecular sciences |
| record_format | pubmed |
| spellingShingle | Discovery of a Novel Anticoagulant Cystine Knot Peptide from Spider Venom Gland Transcriptome. Gao, Jinai Yang, Di Wang, Wanting Huang, Xiaoshan Guo, Ruiyin Cao, Kaixun Lu, Qiumin Wang, Ziyi Lai, Ren Li, Juan Animals Spider Venoms Anticoagulants Transcriptome Mice Humans Peptides Thrombosis Blood Coagulation Male Cystine Knot Motifs Discovery of a Novel Anticoagulant Cystine Knot Peptide from Spider Venom Gland Transcriptome. Gao, Jinai Yang, Di Wang, Wanting Huang, Xiaoshan Guo, Ruiyin Cao, Kaixun Lu, Qiumin Wang, Ziyi Lai, Ren Li, Juan Animals Spider Venoms Anticoagulants Transcriptome Mice Humans Peptides Thrombosis Blood Coagulation Male Cystine Knot Motifs The development of effective anticoagulants remains a critical need in modern medicine, particularly for preventing and treating thromboembolic disorders, such as arterial thrombosis and deep vein thrombosis (DVT), as well as complications like ischemic stroke. This study identifies a cysteine-knotted peptide GC38 (sequence: GCSGKGARCAPSKCCSGLSCGRHGGNMYKSCEWNWKTG) derived from the venom gland transcriptome of the sp. spider, which exerts thrombus-inhibitory effects by potentiating activated protein C (APC) activity. In vitro assays reveal that GC38 enhances APC activity, prolongs plasma clotting time, and shows no significant cytotoxicity or hemolytic activity. Mechanistically, GC38 interacts allosterically with APC; biolayer interferometry (BLI) confirms this direct interaction, with a dissociation constant of 6.16 μM. Additionally, three in vivo thrombosis models (FeCl-induced arterial occlusion, stasis-induced DVT, and cortical photothrombotic stroke) consistently demonstrated that GC38 was effective in alleviating thrombus formation, with tail-bleeding assays confirming its low hemorrhagic risk. Collectively, our findings position GC38 as a pioneering spider venom-derived lead molecule that addresses dual arterial and venous antithrombotic actions. This opens new avenues for developing spider venom-derived peptides as therapeutic agents targeting intravascular coagulation in arteries and veins. |
| title | Discovery of a Novel Anticoagulant Cystine Knot Peptide from Spider Venom Gland Transcriptome. |
| topic | Animals Spider Venoms Anticoagulants Transcriptome Mice Humans Peptides Thrombosis Blood Coagulation Male Cystine Knot Motifs |
| url | https://pubmed.ncbi.nlm.nih.gov/41155448/ |