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The wasp venom antimicrobial peptide polybia‐CP and its synthetic derivatives display antiplasmodial and anticancer properties
Bioengineering & Translational Medicine ( IF 7.4 ) Pub Date : 2020-05-16 , DOI: 10.1002/btm2.10167
Marcelo D. T. Torres 1 , Adriana F. Silva 2, 3 , Gislaine P. Andrade 2 , Cibele N. Pedron 2 , Giselle Cerchiaro 2 , Anderson O. Ribeiro 2 , Vani X. Oliveira 2, 4 , Cesar Fuente‐Nunez 1
Affiliation  

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.

中文翻译:

黄蜂毒液抗菌肽polybia-CP及其合成衍生物具有抗血浆和抗癌特性

黄蜂毒液衍生的抗菌肽polybia-CP先前已显示出有效的抗菌活性,但它也具有很高的毒性。以前,我们使用物理化学指导的肽设计策略,在保留甚至增强其抗菌性能的同时扭转了其毒性。在这里,我们报告了多比亚-CP和衍生物的其他一些意外生物学特性,即它们靶向疟原虫子孢子的能力和癌细胞。我们利用物理化学指导的方法来鉴定充当功能热点的功能,从而使这些肽成为抗血浆和抗癌剂的可行之选。螺旋含量和净正电荷被确定为抗血浆活性的关键结构和物理化学决定因素。除了螺旋性和净电荷外,还发现与polybia-CP及其衍生物的疏水性相关的特性对靶向癌细胞同样重要。我们证明,通过调节这些理化参数,可以设计具有增强的亚微摩尔抗血浆活性和微摩尔抗癌活性的合成肽。这项研究揭示了Polybia-CP和类似物的新颖且以前未描述的功能。另外,
更新日期:2020-05-16
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