Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators

Howes, J.M., Theakston, R.David G. and Laing, Gavin (2007) 'Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators'. Toxicon, Vol 49, Issue 5, pp. 734-739.

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Abstract

Envenoming by the West African saw-scaled viper, Echis ocellatus resembles that of most vipers, in that it results in local blistering, necrosis and sometimes life-threatening systemic haemorrhage. While effective against systemic envenoming, current antivenoms have little or no effect against local tissue damage. The major mediators of local venom pathology are the zinc-dependant snake venom metalloproteinases (SVMPs). The high degree of structural and functional homology between SVMPs and their mammalian relatives the matrix metalloproteinases (MMPs) suggests that substrate/inhibitor interactions between these subfamilies are likely to be analogous. In this study, four recently developed MMP inhibitors (MMPIs) (Marimastat, AG-3340, CGS-270 23A and Bay-12 9566) are evaluated in addition to three metal ion chelators (EDTA, TPEN and BAPTA) for their ability to inhibit the haemorrhagic activities of the medically important E. ocellatus venom and one of its haemorrhagic SVMPs, EoVMP2. As expected, the metal ion chelators significantly inhibited the haemorrhagic activities of both whole E. ocellatus venom and EoVMP2, while the synthetic MMPIs show more variation in their efficacies. These variations suggest that individual MMPIs show specificity towards SVMPs and that their application to the neutralization of local haemorrhage may require a synthetic MMPI mixture, ensuring that a close structural component for each SVMP is represented. (c) 2006 Elsevier Ltd. All rights reserved.

Item Type:	Article
Uncontrolled Keywords:	snake venom echis haemorrhagic activity metalloproteinase peptide inhibitor chelator local tissue-damage bothrops-asper terciopelo matrix metalloproteinases cancer-therapy batimastat purification immunization pathogenesis cana(2)edta atrolysin
Subjects:	WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.toxicon.2006.11.020
Depositing User:	Ms Julia Martin
Date Deposited:	15 Dec 2010 16:41
Last Modified:	06 Feb 2018 13:01
URI:	https://archive.lstmed.ac.uk/id/eprint/1219

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