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| Main Authors: | , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
European journal of pharmacology
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40716633/ |
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Table of Contents:
- Identification and functional analysis of a novel potent anti-angiogenesis peptide SAIF-B2 derived from shark cartilage. Xie, Junye Xiao, Yujie Zhang, Yibo Hong, An Chen, Xiaojia Animals Humans Angiogenesis Inhibitors Zebrafish Human Umbilical Vein Endothelial Cells Sharks Cell Proliferation Cell Movement Molecular Docking Simulation Peptides Cartilage Neovascularization, Physiologic Neovascularization, Pathologic Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2 Carcinoma, Hepatocellular Signal Transduction Marine-derived bioactive molecules represent promising candidates for lead drug development. Structural optimisation of these lead drugs significantly enhances their suitability as drugs, setting the framework for large-scale manufacturing. We previously identified shark-derived angiogenesis inhibition factor (SAIF), a 33 amino acid peptide from shark cartilage, which has anti-angiogenic activity but has inadequate in vivo stability, thereby limiting clinical translation. In this study, we employed a computational molecular docking-guided truncation strategy to optimise and screen SAIF-B2, a truncated 20 amino acid peptide. SAIF-B2 improved plasma proteolytic stability by 67 % while maintaining strong affinity for vascular endothelial growth factor receptor 2 and vascular endothelial growth factor A. Functionally, SAIF-B2 decreased HUVEC proliferation, migration and tube formation in a dose-dependent manner, resulting in G1/S phase cell cycle arrest. SAIF-B2 markedly suppressed neovascularisation in the chick chorioallantoic membrane assay and zebrafish models. Transcriptomic analysis revealed its anti-angiogenic mechanism, which involves the suppression of VEGF, MAPK, and PI3K-AKT signalling pathways. Notably, SAIF-B2 exhibited potent anti-tumour effects in a hepatocellular carcinoma model and effectively inhibited pathological corneal neovascularisation. These findings establish SAIF-B2 as a superior marine-derived anti-angiogenic peptide with enhanced stability (67 % improvement), smaller molecular weight, and lower production costs than those of its parent molecule. This multi-target therapeutic agent shows significant potential for treating angiogenesis-driven pathologies, including malignancies and macular degeneration, thereby warranting further preclinical development.