Hitchhiking with Nature : exploring snake venom peptides to fight cancer and superbugs
This work describes the discovery and optimization of efficient, selective, cost-effective and proteolytic-resistant antimicrobial and antitumoral peptides. To this end, we first identified novel cathelicidin-related peptides from the venom gland of South American pit vipers, collectively named vipe...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/668411 |
| Acceso en línea: | http://hdl.handle.net/10803/668411 |
| Access Level: | acceso abierto |
| Palabra clave: | Antimicrobial peptides Anticancer peptides Peptide membrane interaction Peptide optimization Peptide degradation Péptidos antimicrobianos Péptidos antitumorales Interacciones péptido-membrana Optimización de péptidos Proteólisi 615 |
| Sumario: | This work describes the discovery and optimization of efficient, selective, cost-effective and proteolytic-resistant antimicrobial and antitumoral peptides. To this end, we first identified novel cathelicidin-related peptides from the venom gland of South American pit vipers, collectively named vipericidins. In particular, crotalicidin (Ctn), a 34-mer helical peptide from the Crotalus durissus terrificus venom, highlighted due to its promising antimicrobial and antitumoral properties. Its fragment Ctn[15-34] also stood out due to its overall preserved activity, improved selectivity, serum stability and significant size reduction. Their mechanisms of action were stepwise characterized against Escherichia coli and a leukemic cell line. The unusually high lifespan of Ctn[15-34] in serum was also investigated to ascertain its structural determinants and molecular interaction with serum proteins. Altogether, this thesis proposes two novel bioactive peptides as potential drug candidates to fight bacterial infections and cancer, particularly leukemia. Beyond specific results, this thesis provides a set of valuable methodologies to discover, optimize and evaluate bioactive molecules from natural sources. |
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