Applications Of Snake Toxins In Biomedicine

This chapter provides an overview of the application of snake toxins in biomedicine and the use of snake venom proteins that are employed in diagnostic testing procedures in clinical laboratories around the world. The chapter is subdivided into several different areas, and a summary of work ongoing in those areas is presented to provide the reader an overview of the importance of snake venom proteins and peptides in biomedicine. The subdivision of the chapter is as follows: sections "Use of Neurotoxic Snake Venom Proteins/Peptides in Biomedicine," "Use of Snake Venom Proteins/Peptides as Antihypertensive Agents," " Use of Snake Venom Proteins/Peptides in Cancer Therapy," "Uses of Snake Venom Proteins/Peptides in Cardiovascular Disease," and "Diagnostic Use of Snake Venom Proteins."Included in section "Use of Neurotoxic Snake Venom Proteins/Peptides in Biomedicine" are investigations into the application of venom peptides for pain relief, preliminary studies on the use of detoxified cobra toxin for treatment of multiple sclerosis, and preliminary investigations on the application of cobra toxin for treatment of mesothelioma. Section "Use of Snake Venom Proteins/Peptides as Antihypertensive Agents" deals with the development of the drug captopril, an angiotensin-converting enzyme inhibitor, whose structure was based on a small peptide isolated from the Brazilian pit viper (Bothrops jararaca) venom. Section "Use of Snake Venom Proteins/Peptides in Cancer Therapy" primarily focuses on in vivo activities of a class of snake venom peptides known as disintegrins. The anticancer/antiangiogenic activity of the disintegrins is based on their interactions with a subset of integrins involved in cancer and angiogenic endothelial cell motility. A brief discussion is given for cilengitide, a cyclic pentapeptide whose structure is based on the venom disintegrin Arg-Gly-Asp motif. Not discussed in this section are a variety of other anticancer agents found in snake venom, but whose potential toxicity and side effects have not been explored in sufficient depth to merit being considered of interest for clinical application. In section "Uses of Snake Venom Proteins/Peptides in Cardiovascular Disease," the discussion is focused on the use of inhibitors of platelet integrin alpha IIb beta 3, the fibrinogen receptor, which is involved in platelet aggregation, and the development of these inhibitors based on snake venom disintegrins from which their structures evolved. Also discussed in this section are the snake venom metalloproteinases with fibrinolytic activity and the clinical development of one of these for the treatment of arterial occlusion and stroke. The section continues with an analysis of snake venom defibrinogenating enzymes and their use for a number of thrombotic disorders such as deep vein thrombosis and acute ischemic stroke. Finally, snake venom inhibitors of blood serine proteinases and their application in biomedicine are discussed. In section " Diagnostic Use of Snake Venom Proteins," the diagnostic use of a number of different venom components is discussed including the protein C activator, ProTac (R), from pit viper venom; the prothrombinase-induced clotting time, which relies on the factor V activator from Russell's viper venom; the use of noscarin, a prothrombin activator from the Australian tiger snake venom, in the activated protein C resistance test to determine the presence of factor V Leiden in patients' blood samples; and several other diagnostic tests that employ venom fractions are also discussed.