Purification and Characterization of a Novel Antiplatelet Peptide from Deinagkistrodon acutus Venom

Abstract

Animal venoms are considered as one of the most important sources for drug development. Deinagkistrodon acutus 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 D. acutus 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.

DAKS1, a Kunitz Scaffold Peptide from the Venom Gland of Deinagkistrodon acutus Prevents Carotid-Artery and Middle-Cerebral-Artery Thrombosis via Targeting Factor XIa

“…Snake venoms are a weapon library formed through millions of years of adaptive evolution for their prey and defense in the natural environment [40,41]. D. acutus is a poisonous snake, and its envenomation incurs hemorrhage and thrombus formation [42]. The venom contains an activator or inhibitor of the coagulation system, especially Kunitz/BPTI-type serine protease inhibitors [43,44].…”

Recent Advances in Nanomaterials for Diagnosis, Treatments, and Neurorestoration in Ischemic Stroke

“…By mimicking these biological entities such as viruses, exosomes, platelets, erythrocytes, and leukocytes, human endogenous cell-derived biomimetic drug carriers offer higher biosafety and targeting capabilities than artificial carriers (Parodi et al, 2017 ). Platelets play a key role in thrombosis (Kong et al, 2018 ). Natural platelets (PLT) can target adhesion to damaged vessels during thrombosis, so Li et al ( 2018 ) fabricated a biomimetic nanocarrier containing a PLT membrane envelope containing L-arginine and γ-Fe 2 O 3 magnetic nanoparticles (PAMN) for thrombus-targeted L-arginine delivery and in situ production of nitric oxide (NO; Figure 5A ).…”

<i>In </i><i>Silico</i> Screening of Potential Inhibitors against dPLA2 from Named Chinese Herbs for Identification of Compounds with Antivenom Effects Due to <i>Deinagkistrodon acutus </i>Snake Bites

“…Jin H and coworkers found that the most abundant constituent of the Deinagkistrodon acutus venom was phospholipases A2 (30.0%), snaclec (21.0%), antithrombin (17.8%), thrombin (8.1%) and metalloproteinases (4.2%) [8]. Deinagkistrodon acutus phospholipases A2 (dPLA2) that calcium ion dependent plays an essential role in the pathological process on the patient [7] [9]. Since this protease catalyzes the hydrolysis of the fatty acid ester at the sn-2 position of phospholipids releasing lysophospholipids and fatty acids [10] [11], and exerts a wide variety of relevant toxic actions such as myotoxic, neurotoxic, cardiotoxic, anticoagulant, cytotoxic, edematogenic, and proinflammatory effects [12] [13].…”