Anti-thrombotic agents derived from snake venom proteins

Abstract

Snake venoms affect blood coagulation and platelet function in a complex manner. However, two classes of venom proteins, snaclecs and disintegrins have been shown to specifically target receptors including GPIb, α2β1, GPVI, CLEC-2 and integrins αIIbβ3, αvβ3, α5β1 expressed on platelets, endothelial cells, phagocytes, tumor cells, thus affecting cell-matrices and cell-cell interactions. Here, we focus on disintegrins, a class of low molecular mass Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptide derived from various viper snake venoms. This review describes the potential applications of disintegrins in field of integrin-related diseases, especially arterial thrombosis, angiogenesis, tumor progression and septic inflammation. In addition, a novel RGD-containing disintegrin TMV-7 is being developed as a safer antithrombotic agent with minimal side effects, such as thrombocytopenia and bleeding.

Harnessing snake venom phospholipases A2 to novel approaches for overcoming antibiotic resistance

“…Fortunately, both academia and industry are changing gears regarding peptide‐based drugs, and market projections accompany this trend. Recent development of anti‐thrombotic agents inspired in snake venom proteins (Huang, Hsu, & Kuo, ) presage a bright future for bioactive peptides derived from such toxins. In particular, identification of new antimicrobial molecules from natural sources and hit‐to‐lead‐to‐candidate efforts thereof are crucial to keep pace in the fight against resistant pathogens.…”

Toxin Fused with SUMO Tag: A New Expression Vector Strategy to Obtain Recombinant Venom Toxins with Easy Tag Removal inside the Bacteria

“…Therefore, these molecules can interfere in important processes involved in carcinogenesis, tumor growth and invasion, which makes them interesting molecules for cancer treatment [40]. In platelets, they can inhibit aggregation by competitively blocking fibrinogen binding to α IIb β 3 receptors, representing an important tool as anti-thrombotic agents [13]. …”

“…Snake toxins have also been expressed into E. coli and this approach has allowed the characterization of toxins with anti-thrombotic [13], anticancer [14], anti-inflammatory [15], antimicrobial activities [16] as well as fused toxins for the development of serotherapy against envenomation [17]. However, when a recombinant protein is synthesized in E. coli , the microenvironment is different from that of the original source, which may lead to protein aggregation, known as inclusion bodies [18].…”

Toxins Are an Excellent Source of Therapeutic Agents against Cardiovascular Diseases

“…60,64 Since integrins play important roles in cell growth, adhesion, migration, tissue organization, hemostasis, and inflammatory responses, 46,47 integrin inhibitors are an attractive source of inspiration for the development cardiovascular, cancer, inflammatory, and osteoporosis therapeutics. 65 Aggregation of platelets after activation mainly proceeds through the interactions between GPIIb/IIIa (i.e., integrin α IIb β 3 ), fibrinogen, and VWF. 66 Many RGD-or KGD-containing snake venom disintegrins are found to be potent inhibitors of this interaction, preventing platelet aggregation.…”