The wasp venom antimicrobial peptide polybia‐CP and its synthetic derivatives display antiplasmodial and anticancer properties
Abstract The wasp venom‐derived antimicrobial peptide polybia‐CP has been previously shown to exhibit potent antimicrobial activity, but it is also highly toxic. Previously, using a physicochemical‐guided peptide design strategy, we reversed its toxicity while preserving and even enhancing its antib...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-09-01
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| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10167 |
| _version_ | 1811269845133557760 |
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| author | Marcelo D. T. Torres Adriana F. Silva Gislaine P. Andrade Cibele N. Pedron Giselle Cerchiaro Anderson O. Ribeiro Vani X. Oliveira Jr Cesar de laFuente‐Nunez |
| author_facet | Marcelo D. T. Torres Adriana F. Silva Gislaine P. Andrade Cibele N. Pedron Giselle Cerchiaro Anderson O. Ribeiro Vani X. Oliveira Jr Cesar de laFuente‐Nunez |
| author_sort | Marcelo D. T. Torres |
| collection | DOAJ |
| description | Abstract The wasp venom‐derived antimicrobial peptide polybia‐CP has been previously shown to exhibit potent antimicrobial activity, but it is also highly toxic. Previously, using a physicochemical‐guided peptide design strategy, we reversed its toxicity while preserving and even enhancing its antibacterial properties. Here, we report on several additional unanticipated biological properties of polybia‐CP and derivatives, namely their ability to target Plasmodium sporozoites and cancer cells. We leverage a physicochemical‐guided approach to identify features that operate as functional hotspots making these peptides viable antiplasmodial and anticancer agents. Helical content and net positive charge are identified as key structural and physicochemical determinants for antiplasmodial activity. In addition to helicity and net charge, hydrophobicity‐related properties of polybia‐CP and derivatives were found to be equally critical to target cancer cells. We demonstrate that by tuning these physicochemical parameters, it is possible to design synthetic peptides with enhanced submicromolar antiplasmodial potency and micromolar anticancer activity. This study reveals novel and previously undescribed functions for Polybia‐CP and analogs. Additionally, we demonstrate that a physicochemical‐guided rational design strategy can be used for identifying functional hotspots in peptide molecules and for tuning structure–function to generate novel and potent new‐to‐nature therapies. |
| first_indexed | 2024-04-12T21:49:20Z |
| format | Article |
| id | doaj.art-0a8c8398c5b543c586bd456a53e8e960 |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-04-12T21:49:20Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-0a8c8398c5b543c586bd456a53e8e9602022-12-22T03:15:31ZengWileyBioengineering & Translational Medicine2380-67612020-09-0153n/an/a10.1002/btm2.10167The wasp venom antimicrobial peptide polybia‐CP and its synthetic derivatives display antiplasmodial and anticancer propertiesMarcelo D. T. Torres0Adriana F. Silva1Gislaine P. Andrade2Cibele N. Pedron3Giselle Cerchiaro4Anderson O. Ribeiro5Vani X. Oliveira Jr6Cesar de laFuente‐Nunez7Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, Penn Institute for Computational Science, and Department of Bioengineering University of Pennsylvania Philadelphia Pennsylvania USACentro de Ciências Naturais e Humanas Universidade Federal do ABC Santo André SP BrazilCentro de Ciências Naturais e Humanas Universidade Federal do ABC Santo André SP BrazilCentro de Ciências Naturais e Humanas Universidade Federal do ABC Santo André SP BrazilCentro de Ciências Naturais e Humanas Universidade Federal do ABC Santo André SP BrazilCentro de Ciências Naturais e Humanas Universidade Federal do ABC Santo André SP BrazilCentro de Ciências Naturais e Humanas Universidade Federal do ABC Santo André SP BrazilMachine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, Penn Institute for Computational Science, and Department of Bioengineering University of Pennsylvania Philadelphia Pennsylvania USAAbstract The wasp venom‐derived antimicrobial peptide polybia‐CP has been previously shown to exhibit potent antimicrobial activity, but it is also highly toxic. Previously, using a physicochemical‐guided peptide design strategy, we reversed its toxicity while preserving and even enhancing its antibacterial properties. Here, we report on several additional unanticipated biological properties of polybia‐CP and derivatives, namely their ability to target Plasmodium sporozoites and cancer cells. We leverage a physicochemical‐guided approach to identify features that operate as functional hotspots making these peptides viable antiplasmodial and anticancer agents. Helical content and net positive charge are identified as key structural and physicochemical determinants for antiplasmodial activity. In addition to helicity and net charge, hydrophobicity‐related properties of polybia‐CP and derivatives were found to be equally critical to target cancer cells. We demonstrate that by tuning these physicochemical parameters, it is possible to design synthetic peptides with enhanced submicromolar antiplasmodial potency and micromolar anticancer activity. This study reveals novel and previously undescribed functions for Polybia‐CP and analogs. Additionally, we demonstrate that a physicochemical‐guided rational design strategy can be used for identifying functional hotspots in peptide molecules and for tuning structure–function to generate novel and potent new‐to‐nature therapies.https://doi.org/10.1002/btm2.10167antimicrobial peptidesPolybia‐CPrational designstructure‐guided designwasp venom peptide |
| spellingShingle | Marcelo D. T. Torres Adriana F. Silva Gislaine P. Andrade Cibele N. Pedron Giselle Cerchiaro Anderson O. Ribeiro Vani X. Oliveira Jr Cesar de laFuente‐Nunez The wasp venom antimicrobial peptide polybia‐CP and its synthetic derivatives display antiplasmodial and anticancer properties Bioengineering & Translational Medicine antimicrobial peptides Polybia‐CP rational design structure‐guided design wasp venom peptide |
| title | The wasp venom antimicrobial peptide polybia‐CP and its synthetic derivatives display antiplasmodial and anticancer properties |
| title_full | The wasp venom antimicrobial peptide polybia‐CP and its synthetic derivatives display antiplasmodial and anticancer properties |
| title_fullStr | The wasp venom antimicrobial peptide polybia‐CP and its synthetic derivatives display antiplasmodial and anticancer properties |
| title_full_unstemmed | The wasp venom antimicrobial peptide polybia‐CP and its synthetic derivatives display antiplasmodial and anticancer properties |
| title_short | The wasp venom antimicrobial peptide polybia‐CP and its synthetic derivatives display antiplasmodial and anticancer properties |
| title_sort | wasp venom antimicrobial peptide polybia cp and its synthetic derivatives display antiplasmodial and anticancer properties |
| topic | antimicrobial peptides Polybia‐CP rational design structure‐guided design wasp venom peptide |
| url | https://doi.org/10.1002/btm2.10167 |
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