School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Street, Nanjing 210009, China.
Toxins (Basel). 2018 Aug 16;10(8):332. doi: 10.3390/toxins10080332.
Animal venoms are considered as one of the most important sources for drug development. ac is famous for its toxicity to the human hematological system and envenomed patients develop a coagulation disorder with the symptoms of hemorrhage and microthrombi formation. The purpose of this study was to separate antiplatelet peptides from venom using a combination of an ultrafiltration technique and reversed-phase high performance liquid chromatography (HPLC), which was guided by monitoring antiplatelet aggregation bioactivity. A novel octa-peptide named DAA-8 was found. This peptide inhibited protease-activated receptor1 (PAR-1) agonist (SFLLRN-NH₂) induced platelet aggregation and it also inhibited platelet aggregation induced by thrombin, ADP, and collagen. Furthermore, DAA-8 showed significant antithrombotic activity and resulted in a slightly increased bleeding risk in vivo. This is the first report of a peptide derived from snake venom, which inhibited PAR-1 agonist-induced platelet aggregation. This peptide may provide a template to design a new PAR-1 inhibitor.
动物毒液被认为是药物开发的最重要来源之一。a 蛇以其对人类血液系统的毒性而闻名，被毒液咬伤的患者会出现凝血障碍，表现为出血和微血栓形成。本研究旨在使用超滤技术和反相高效液相色谱（HPLC）相结合的方法从毒液中分离抗血小板肽，该方法通过监测抗血小板聚集生物活性进行指导。发现了一种新型的八肽，命名为 DAA-8。该肽抑制蛋白酶激活受体 1（PAR-1）激动剂（SFLLRN-NH₂）诱导的血小板聚集，也抑制凝血酶、ADP 和胶原诱导的血小板聚集。此外，DAA-8 在体内显示出显著的抗血栓活性，并导致出血风险略有增加。这是首次报道从蛇毒液中衍生的肽可抑制 PAR-1 激动剂诱导的血小板聚集。该肽可能为设计新型 PAR-1 抑制剂提供模板。
