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Open AccessArticle

Potential of Matrix Metalloproteinase Inhibitors for the Treatment of Local Tissue Damage Induced by a Type P-I Snake Venom Metalloproteinase

1
Programa de Ofidismo/Escorpionismo, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín 050010, Colombia
2
Institute of Computational Comparative Medicine, Kansas State University, Manhattan, KS 66506, USA
*
Authors to whom correspondence should be addressed.
Received: 30 October 2019 / Revised: 7 December 2019 / Accepted: 12 December 2019 / Published: 20 December 2019
(This article belongs to the Special Issue Novel Strategies for the Diagnosis and Treatment of Snakebites)
Snake bite envenoming is a public health problem that was recently included in the list of neglected tropical diseases of the World Health Organization. In the search of new therapies for the treatment of local tissue damage induced by snake venom metalloproteinases (SVMPs), we tested the inhibitory activity of peptidomimetic compounds designed as inhibitors of matrix metalloproteinases on the activities of the SVMP Batx-I, from Bothrops atrox venom. The evaluated compounds show great potential for the inhibition of Batx-I proteolytic, hemorrhagic and edema-forming activities, especially the compound CP471474, a peptidomimetic including a hydroxamate zinc binding group. Molecular dynamics simulations suggest that binding of this compound to the enzyme is mediated by the electrostatic interaction between the hydroxamate group and the zinc cofactor, as well as contacts, mainly hydrophobic, between the side chain of the compound and amino acids located in the substrate binding subsites S1 and S1 . These results show that CP471474 constitutes a promising compound for the development of co-adjuvants to neutralize local tissue damage induced by snake venom metalloproteinases. View Full-Text
Keywords: local tissue damage; molecular dynamics; inhibitors; peptidomimetics; snake venom metalloproteinase; free energy calculation local tissue damage; molecular dynamics; inhibitors; peptidomimetics; snake venom metalloproteinase; free energy calculation
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MDPI and ACS Style

Preciado, L.M.; Pereañez, J.A.; Comer, J. Potential of Matrix Metalloproteinase Inhibitors for the Treatment of Local Tissue Damage Induced by a Type P-I Snake Venom Metalloproteinase. Toxins 2020, 12, 8.

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