Peptide name : Polybia-CP

Source/Organism : Neotropical social wasp, Swarm-founding polistine wasp

Linear/Cyclic : Not found

Chirality : L

Peptide length: 12

C-terminal modification: Not found

N-terminal modification : Free

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : Not found

Cell line : Not found

Cancer type : Breast cancer

Other activity : Anti-microbial activity

Amino acid composition bar chart :

Molecular mass : 1240.5746 Dalton

Aliphatic index : 2.275

Instability index : 27.1167

Hydrophobicity (GRAVY) : 1.8167

Isoelectric point : 8.7501

Charge (pH 7) : 0.7591

Aromaticity : 0

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : 3

hydrophobic moment : 1.3471

Missing amino acid : C,R,W,H,Q,P,M,E,F,D,Y,N,A,V

Most occurring amino acid : L

Most occurring amino acid frequency : 5

Least occurring amino acid : T

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0.2, 0.6)

SMILES Notation: CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)O)[C@@H](C)CC)[C@@H](C)O

1 : Souza BM, et al. Structural and functional characterization of two novel peptide toxins isolated from the venom of the social wasp Polybia paulista. Peptides. 2005; 26:2157-64. doi: 10.1016/j.peptides.2005.04.026

2 : Wang K, et al. Membrane-active action mode of polybia-CP, a novel antimicrobial peptide isolated from the venom of Polybia paulista. Antimicrob Agents Chemother. 2012; 56:3318-23. doi: 10.1128/AAC.05995-11

3 : Wang K, et al. Membrane perturbation action mode and structure-activity relationships of Protonectin, a novel antimicrobial peptide from the venom of the neotropical social wasp Agelaia pallipes pallipes. Antimicrob Agents Chemother. 2013; 57:4632-9. doi: 10.1128/AAC.02311-12

4 : Torres MDT, et al. Structure-function-guided exploration of the antimicrobial peptide polybia-CP identifies activity determinants and generates synthetic therapeutic candidates. Commun Biol. 2018; 1:221. doi: 10.1038/s42003-018-0224-2

5 : Freire KA, et al. Wasp venom peptide as a new antichagasic agent. Toxicon. 2020; 181:71-78. doi: 10.1016/j.toxicon.2020.04.099

6 : Wang K, et al. Novel cytotoxity exhibition mode of polybia-CP, a novel antimicrobial peptide from the venom of the social wasp Polybia paulista. Toxicology. 2011; 288:27-33. doi: 10.1016/j.tox.2011.06.014

Paper title : Structural and functional characterization of two novel peptide toxins isolated from the venom of the social wasp Polybia paulista.

Doi : https://doi.org/10.1016/j.peptides.2005.04.026

Abstract : Two novel inflammatory peptides were isolated from the venom of the social wasp Polybia paulista. They had their molecular masses determined by ESI-MS and their primary sequences were elucidated by Edman degradation chemistry as: Polybia-MPI: I D W K K L L D A A K Q I L-NH2 (1654.09 Da), Polybia-CP: I L G T I L G L L K S L-NH2 (1239.73 Da). Both peptides were functionally characterized by using Wistar rat cells. Polybia-MPI is a mast cell lytic peptide, which causes no hemolysis to rat erythrocytes and presents chemotaxis for polymorphonucleated leukocytes (PMNL) and with potent antimicrobial action both against Gram-positive and Gram-negative bacteria. Polybia-CP was characterized as a chemotactic peptide for PMNL cells, presenting antimicrobial action against Gram-positive bacteria, but causing no hemolysis to rat erythrocytes and no mast cell degranulation activity at physiological concentrations.

Paper title : Membrane-active action mode of polybia-CP, a novel antimicrobial peptide isolated from the venom of Polybia paulista.

Doi : https://doi.org/10.1128/AAC.05995-11

Abstract : The extensive use of antibiotics in medicine, the food industry, and agriculture has resulted in the frequent emergence of multidrug-resistant bacteria, which creates an urgent need for new antibiotics. It is now widely recognized that antimicrobial peptides (AMPs) could play a promising role in fighting multidrug-resistant bacteria. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and studied its action mode of antibacterial activity. Our results revealed that polybia-CP has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. The results from both the real bacterial membrane and the in vitro model membrane showed that polybia-CP is membrane active and that its action target is the membrane of bacteria. It is difficult for bacteria to develop resistance to polybia-CP, which may thus offer a new strategy for defending against resistant bacteria in medicine and the food and farming industries.

Paper title : Membrane perturbation action mode and structure-activity relationships of Protonectin, a novel antimicrobial peptide from the venom of the neotropical social wasp Agelaia pallipes pallipes.

Doi : https://doi.org/10.1128/AAC.02311-12

Abstract : With the extensive use of antibiotics, multidrug-resistant bacteria emerge frequently. New antimicrobial agents with novel modes of action are urgently needed. It is now widely accepted that antimicrobial peptides (AMPs) could be promising alternatives to conventional antibiotics. In this study, we aimed to study the antimicrobial activity and mechanism of action of protonectin, a cationic peptide from the venom of the neotropical social wasp Agelaia pallipes pallipes. We demonstrated that protonectin exhibits potent antimicrobial activity against a spectrum of bacteria, including multidrug-resistant strains. To further understand this mechanism, the structural features of protonectin and its analogs were studied by circular dichroism (CD). The CD spectra demonstrated that protonectin and its natural analog polybia-CP formed a typical α-helical conformation in the membrane-mimicking environment, while its proline-substituted analog had much lower or even no α-helix conformation. Molecular dynamics simulations indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity. In conclusion, protonectin exhibits potent antimicrobial activity by disruption of the integrity of the bacterial membrane, and its α-helical confirmation in the membrane is essential for this action.

Paper title : Structure-function-guided exploration of the antimicrobial peptide polybia-CP identifies activity determinants and generates synthetic therapeutic candidates.

Doi : https://doi.org/10.1038/s42003-018-0224-2

Abstract : Antimicrobial peptides (AMPs) constitute promising alternatives to classical antibiotics for the treatment of drug-resistant infections, which are a rapidly emerging global health challenge. However, our understanding of the structure-function relationships of AMPs is limited, and we are just beginning to rationally engineer peptides in order to develop them as therapeutics. Here, we leverage a physicochemical-guided peptide design strategy to identify specific functional hotspots in the wasp-derived AMP polybia-CP and turn this toxic peptide into a viable antimicrobial. Helical fraction, hydrophobicity, and hydrophobic moment are identified as key structural and physicochemical determinants of antimicrobial activity, utilized in combination with rational engineering to generate synthetic AMPs with therapeutic activity in a mouse model. We demonstrate that, by tuning these physicochemical parameters, it is possible to design nontoxic synthetic peptides with enhanced sub-micromolar antimicrobial potency in vitro and anti-infective activity in vivo. We present a physicochemical-guided rational design strategy to generate peptide antibiotics.

Paper title : Wasp venom peptide as a new antichagasic agent.

Doi : https://doi.org/10.1016/j.toxicon.2020.04.099

Abstract : Chagas disease is caused by Trypanosoma cruzi and affects approximately 10 million people a year worldwide. The only two treatment options, benznidazole and nifurtimox, have low efficacy and high toxicity towards human cells. Mastoporan peptide (MP) a small cationic AMP from the venom of the wasp Polybia paulista has been reported as a potent trypanocidal agent. Thus, we evaluated the antichagasic effect of another AMP from the venom of the same wasp Polybia paulista, polybia-CP (ILGTILGLLSKL-NH₂), and investigated its mechanism of action against different stages of the trypanosomal cells life cycle. Polybia-CP was tested against the epimastigote, trypomastigote and amastigote forms of the T. cruzi Y strain (benznidazole-resistant strain) and inhibited the development of these forms. We also assessed the selectivity of the AMP against mammalian cells by exposing LLC-MK2 cells to polybia-CP, the peptide presented a high selectivity index (>106). The mechanism of action of polybia-CP on trypanosomal cells was investigated by flow cytometry, scanning electron microscopy (SEM) and enzymatic assays with T. cruzi GAPDH (tcGAPDH), enzyme that catalyzes the sixth step of glycolysis. Polybia-CP induced phosphatidylserine exposure, it also increased the formation of reactive species of oxigen (ROS) and reduced the transmembrane mitochondrial potential. Polybia-CP also led to cell shrinkage, evidencing apoptotic cell death. We did not observe the inhibition of tcGAPDH or autophagy induction. Altogether, polybia-CP has shown the features of a promising template for the development of new antichagasic agents.

Paper title : Novel cytotoxity exhibition mode of polybia-CP, a novel antimicrobial peptide from the venom of the social wasp Polybia paulista.

Doi : https://doi.org/10.1016/j.tox.2011.06.014

Abstract : Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. It has an amphipathic sequence ILGTILGLLKSL-NH(2) and possesses potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this study we synthesized polybia-CP, studied its cytotoxity on tumor cells and proposed its possible mechanism. Our results revealed that polybia-CP exerts its cytotoxic efficacy by disrupting the integrity of cell membrane. Furthermore, molecular dynamics (MD) simulations were employed to investigate the mechanism of membrane perturbation. Both the MD simulations and the experimental data indicated that polybia-CP takes a standard α-helix conformation in the membrane. These findings together with the other experimental results support a speculation of mechanism similar to the "carpet" model.