A novel linear depsipeptide enriched with tyrosine-derived moieties, termed apratyramide, was isolated from an apratoxin-producing cyanobacterium. The structure was determined using a combination of NMR spectroscopy, mass spectrometry, and chiral analysis of the acid hydrolyzate and confirmed by total synthesis. Apratyramide up-regulated multiple growth factors at the transcript level in human keratinocyte (HaCaT) cells and induced the secretion of vascular endothelial growth factor A (VEGF-A) from HaCaT cells, suggesting the compound’s potential wound-healing properties through growth factor induction. Transcriptome analysis and sequential validation supported the hypothesis and indicated its mode of action (MOA) through the unfolded protein response (UPR) pathway, which is functionally related to wound healing and angiogenesis. The conditioned medium of HaCaT cells treated with apratyramide induced angiogenesis in vitro. An ex vivo rabbit corneal epithelial model was applied to confirm the VEGF-A induction in this wound-healing model.

中文翻译：

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Apratyramide，一种海洋衍生的VEGF-A和其他生长因子的肽类刺激物，在伤口愈合中具有潜在的应用价值

从产生一种人毒素的蓝藻细菌中分离了一种新型线性线性二肽肽，该肽富含酪氨酸衍生的部分，称为腺苷酰胺。使用NMR光谱法，质谱法和酸水解产物的手性分析的组合来确定结构，并通过全合成进行确认。安普他酰胺在人类角质形成细胞（HaCaT）细胞的转录水平上调了多种生长因子，并诱导了HaCaT细胞分泌血管内皮生长因子A（VEGF-A），表明该化合物通过生长因子诱导具有潜在的伤口愈合特性。转录组分析和顺序验证支持了这一假说，并通过未折叠的蛋白质反应（UPR）途径表明了其作用方式（MOA），该途径与伤口愈合和血管生成在功能上相关。用吡ty酰胺处理的HaCaT细胞条件培养液可在体外诱导血管生成。应用离体兔角膜上皮模型确认在这种伤口愈合模型中，VEGF-A的诱导。