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Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom

Russell’s viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs) are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment moda...

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Autores principales: Yee, Khin Than, Pitts, Morgan, Tongyoo, Pumipat, Rojnuckarin, Ponlapat, Wilkinson, Mark C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308247/
https://www.ncbi.nlm.nih.gov/pubmed/28042812
http://dx.doi.org/10.3390/toxins9010015
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author Yee, Khin Than
Pitts, Morgan
Tongyoo, Pumipat
Rojnuckarin, Ponlapat
Wilkinson, Mark C.
author_facet Yee, Khin Than
Pitts, Morgan
Tongyoo, Pumipat
Rojnuckarin, Ponlapat
Wilkinson, Mark C.
author_sort Yee, Khin Than
collection PubMed
description Russell’s viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs) are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment modalities for neutralization of the effect of toxins. Two major snake venom metalloproteinases (SVMPs): RVV-X and Daborhagin were purified from Myanmar Russell’s viper venom using a new purification strategy. Using the Next Generation Sequencing (NGS) approach to explore the Myanmar RV venom gland transcriptome, mRNAs of novel tripeptide SVMP inhibitors (SVMPIs) were discovered. Two novel endogenous tripeptides, pERW and pEKW were identified and isolated from the crude venom. Both purified SVMPs showed caseinolytic activity. Additionally, RVV-X displayed specific proteolytic activity towards gelatin and Daborhagin showed potent fibrinogenolytic activity. These activities were inhibited by metal chelators. Notably, the synthetic peptide inhibitors, pERW and pEKW, completely inhibit the gelatinolytic and fibrinogenolytic activities of respective SVMPs at 5 mM concentration. These complete inhibitory effects suggest that these tripeptides deserve further study for development of a therapeutic candidate for Russell’s viper envenomation.
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spelling pubmed-53082472017-02-14 Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom Yee, Khin Than Pitts, Morgan Tongyoo, Pumipat Rojnuckarin, Ponlapat Wilkinson, Mark C. Toxins (Basel) Article Russell’s viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs) are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment modalities for neutralization of the effect of toxins. Two major snake venom metalloproteinases (SVMPs): RVV-X and Daborhagin were purified from Myanmar Russell’s viper venom using a new purification strategy. Using the Next Generation Sequencing (NGS) approach to explore the Myanmar RV venom gland transcriptome, mRNAs of novel tripeptide SVMP inhibitors (SVMPIs) were discovered. Two novel endogenous tripeptides, pERW and pEKW were identified and isolated from the crude venom. Both purified SVMPs showed caseinolytic activity. Additionally, RVV-X displayed specific proteolytic activity towards gelatin and Daborhagin showed potent fibrinogenolytic activity. These activities were inhibited by metal chelators. Notably, the synthetic peptide inhibitors, pERW and pEKW, completely inhibit the gelatinolytic and fibrinogenolytic activities of respective SVMPs at 5 mM concentration. These complete inhibitory effects suggest that these tripeptides deserve further study for development of a therapeutic candidate for Russell’s viper envenomation. MDPI 2016-12-30 /pmc/articles/PMC5308247/ /pubmed/28042812 http://dx.doi.org/10.3390/toxins9010015 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yee, Khin Than
Pitts, Morgan
Tongyoo, Pumipat
Rojnuckarin, Ponlapat
Wilkinson, Mark C.
Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom
title Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom
title_full Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom
title_fullStr Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom
title_full_unstemmed Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom
title_short Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom
title_sort snake venom metalloproteinases and their peptide inhibitors from myanmar russell’s viper venom
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308247/
https://www.ncbi.nlm.nih.gov/pubmed/28042812
http://dx.doi.org/10.3390/toxins9010015
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