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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The wasp venom antimicrobial peptide polybia-CP and its synthetic derivatives display antiplasmodial and anticancer properties

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Torres, Marcelo D. T. [1, 2, 3] ; Silva, Adriana F. [4, 5] ; Andrade, Gislaine P. [4] ; Pedron, Cibele N. [4] ; Cerchiaro, Giselle [4] ; Ribeiro, Anderson O. [4] ; Oliveira Jr, Vani X. ; de la Fuente-Nunez, Cesar [1, 2, 3]
Total Authors: 8
[1] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 - USA
[2] Univ Penn, Dept Psychiat, Machine Biol Grp, Perelman Sch Med, Penn Inst Compu, Inst Biomed Informat, Inst Translat Med & Therapeu, Philadelphia, PA 19104 - USA
[3] Univ Penn, Dept Microbiol, Machine Biol Grp, Perelman Sch Med, Penn Inst Compu, Inst Biomed Informat, Inst Translat Med & Therapeu, Philadelphia, PA 19104 - USA
[4] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil
[5] Univ Fed Sao Paulo, Dept Bioquim, Sao Paulo, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Web of Science Citations: 0

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. (AU)

FAPESP's process: 14/12938-6 - Biologically active peptides against pathogenic micro-organisms
Grantee:Vani Xavier de Oliveira Junior
Support type: Regular Research Grants