Bubik Anja, Sedmak Bojan, Novinec Marko, Lenarcic Brigita, Lah Tamara T
Department of Genetic Toxicology, National Institute of Biology, Vecna pot 111, POB 141, SI-1001 Ljubljana, Slovenia.
Biol Chem. 2008 Oct;389(10):1339-46. doi: 10.1515/BC.2008.153.
Toxic cyanobacterial blooms are a rich source of metabolites having a variety of biological activities. Two main groups of cyclic peptides, depsipeptides and ureido linkage-containing peptides, reportedly inhibit serine peptidases. We characterised their inhibitory properties against selected peptidases and investigated their influence on cell viability. The depsipeptide planktopeptin BL1125 is a strong linear competitive tight-binding inhibitor of leukocyte (K(i)=2.9 nm) and pancreatic (K(i)=7.2 nm) elastase and also of chymotrypsin (K(i)=6.1 nm). Anabaenopeptins B and F show no inhibition against chymotrypsin, but inhibit both elastases. The tested cyclic peptides do not inhibit trypsin, urokinase, kallikrein 1 or cysteine peptidases. All three tested cyanopeptides show no short-term cytotoxicity in concentrations of up to 10 mum, but impair the metabolic activity of normal human astrocytes after prolonged exposure (48-96 h), whereas glioblastoma cells, tumour cells of the same type, are resistant. Strong inhibition and relative selectivity of the tested cyanopeptides suggests that they are potential candidates for application in inflammatory diseases and possibly some types of cancers.
有毒蓝藻水华是具有多种生物活性的代谢物的丰富来源。据报道，两类主要的环肽，即缩肽和含脲基连接的肽，可抑制丝氨酸肽酶。我们表征了它们对选定肽酶的抑制特性，并研究了它们对细胞活力的影响。缩肽浮游菌素BL1125是白细胞弹性蛋白酶（K(i)=2.9纳米）和胰腺弹性蛋白酶（K(i)=7.2纳米）以及胰凝乳蛋白酶（K(i)=6.1纳米）的强线性竞争性紧密结合抑制剂。鱼腥藻肽B和F对胰凝乳蛋白酶无抑制作用，但对两种弹性蛋白酶均有抑制作用。所测试的环肽不抑制胰蛋白酶、尿激酶、激肽释放酶1或半胱氨酸肽酶。所有三种测试的蓝藻肽在浓度高达10微摩尔时均未显示短期细胞毒性，但在长时间暴露（48 - 96小时）后会损害正常人星形胶质细胞的代谢活性，而相同类型的肿瘤细胞胶质母细胞瘤细胞具有抗性。所测试蓝藻肽的强抑制作用和相对选择性表明它们是用于炎症性疾病以及可能某些类型癌症的潜在候选物。
