The use of short peptides or peptide analogs to inhibit proteases has a long history. Metalloproteinases represent an attractive class of protease for inhibition studies due to their central role in numerous physiological processes. The atrolysins represent the main class of snake venom metalloproteinases (SVMPs) found in the Western diamondback rattlesnake (Crotalus atrox). Upon envenomation, these SVMPs rapidly cause tissue necrosis thus allowing other venom components to enter the blood stream. The N. American opossum (Didelphius virginiana) is resistant to up to 65X the expected lethal dose of C. atrox venom. A serum protein from D. virginiana, identified as oprin, was characterized in the early 1990s that forms a reversible complex with several atrolysins, and similar proteins have been characterized from several S. American opossum species. These serum proteins have a characteristic N-terminal sequence (H2N-LKAMDPTPPLWIKTE--) that provides an enticing scaffold to study the structural requirements for these snake venom metalloproteinase inhibitors (SVMPIs). This work will present our efforts to chemically synthesize a peptide library composed of 8-15mers based on the oprin protein sequence and our efforts to probe the structural features necessary for inhibition of atrolysin components from C. atrox.

Development of a peptide library based on naturally occurring proteins from North American opossum (Didelphis virginiana) as potential inhibitors of snake venom metalloproteinases

254th National Meeting (2017)

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