Peptide name : Polybia-mastoparan-I

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

Linear/Cyclic : Not found

Chirality : L

Peptide length: 14

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 : 1654.9899 Dalton

Aliphatic index : 1.535

Instability index : 33.8643

Hydrophobicity (GRAVY) : 0.0643

Isoelectric point : 8.4975

Charge (pH 7) : 0.7593

Aromaticity : 0.071

Molar extinction coefficient (cysteine, cystine): (5500, 5500)

Hydrophobic/hydrophilic ratio : 1.33333333

hydrophobic moment : -1.264

Missing amino acid : C,R,H,T,P,M,E,F,S,Y,N,V,G

Most occurring amino acid : K

Most occurring amino acid frequency : 3

Least occurring amino acid : W

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0.1, 0.4)

SMILES Notation: CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)[C@@H](C)CC

1 : Zhang W, et al. A novel analog of antimicrobial peptide Polybia-MPI, with thioamide bond substitution, exhibits increased therapeutic efficacy against cancer and diminished toxicity in mice. Peptides. 2010; 31:1832-8. doi: 10.1016/j.peptides.2010.06.019

2 : Wang KR, et al. Antitumor effects, cell selectivity and structure-activity relationship of a novel antimicrobial peptide polybia-MPI. Peptides. 2008; 29:963-8. doi: 10.1016/j.peptides.2008.01.015

3 : 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

4 : da Silva AMB, et al. Pro-necrotic Activity of Cationic Mastoparan Peptides in Human Glioblastoma Multiforme Cells Via Membranolytic Action. Mol Neurobiol. 2018; 55:5490-5504. doi: 10.1007/s12035-017-0782-1

5 : Wang KR, et al. Novel mode of action of polybia-MPI, a novel antimicrobial peptide, in multi-drug resistant leukemic cells. Cancer Lett. 2009; 278:65-72. doi: 10.1016/j.canlet.2008.12.027

6 : dos Santos Cabrera MP, et al. Influence of the bilayer composition on the binding and membrane disrupting effect of Polybia-MP1, an antimicrobial mastoparan peptide with leukemic T-lymphocyte cell selectivity. Biochemistry. 2012; 51:4898-908. doi: 10.1021/bi201608d

Paper title : A novel analog of antimicrobial peptide Polybia-MPI, with thioamide bond substitution, exhibits increased therapeutic efficacy against cancer and diminished toxicity in mice.

Doi : https://doi.org/10.1016/j.peptides.2010.06.019

Abstract : Polybia-MPI (MPI), a short cationic α-helical antimicrobial peptide, exhibited excellent anticancer activity and selectivity in vitro in our previous studies. To improve its in vivo application, we synthesized an analog (MPI-1) of MPI by replacing the C terminal amide -[CO-NH(2)] with thioamide -ψ[CS-NH(2)]. Although there is just one atom difference, the MPI-1 exhibited some surprising properties. In vitro studies revealed that MPI-1 exhibited relatively high lytic activity over MPI, whereas its stability to enzymatic degradation in serum was improved remarkably. Despite the enhanced toxicity in vitro, MPI-1 exhibited significantly lower mortality to mice than MPI at 75 mg/kg. Importantly, in vivo anticancer activity study indicated that MPI-1 could remarkably suppress the growth of sarcoma xenograft tumors more efficiently than MPI. Therefore, the significantly improved anticancer activity and predominantly lower in vivo toxicity might allow MPI-1 to be a good candidate for future anticancer treatment.

Paper title : Antitumor effects, cell selectivity and structure-activity relationship of a novel antimicrobial peptide polybia-MPI.

Doi : https://doi.org/10.1016/j.peptides.2008.01.015

Abstract : A novel antimicrobial peptide, polybia-MPI, was purified from the venom of the social wasp Polybia paulista. It has potent antimicrobial activity against both Gram-positive and Gram-negative bacteria, but causing no hemolysis to rat erythrocytes. To date, there is no report about its antitumor effects on any tumor cell lines. In this study we synthesized polybia-MPI and studied its antitumor efficacy and cell selectivity. Our results revealed that polybia-MPI exerts cytotoxic and antiproliferative efficacy by pore formation. It can selectively inhibit the proliferation of prostate and bladder cancer cells, but has lower cytotoxicity to normal murine fibroblasts. In addition, to investigate the structure-activity relationship of polybia-MPI, three analogs in which Leu7, Ala8 or Asp9 replaced by L-Pro were designed and synthesized. L-Pro substitution of Leu7 or Asp9 significantly reduces the content of alpha-helix conformation, and L-Pro substitution of Ala8 can disrupt the alpha-helix conformation thoroughly. The L-Pro substitution induces a significant reduction of antitumor activity, indicating that the alpha-helix conformation of polybia-MPI is important for its antitumor activity. In summary, polybia-MPI may offer a novel therapeutic strategy in the treatment of prostate cancer and bladder cancer, considering its relatively lower cytotoxicity to normal cells.

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 : Pro-necrotic Activity of Cationic Mastoparan Peptides in Human Glioblastoma Multiforme Cells Via Membranolytic Action.

Doi : https://doi.org/10.1007/s12035-017-0782-1

Abstract : Glioblastoma multiforme is the most common and lethal malignant brain tumor. Because of its complexity and heterogeneity, this tumor has become resistant to conventional therapies and the available treatment produces multiple side effects. Here, using multiple experimental approaches, we demonstrate that three mastoparan peptides-Polybia-MP1, Mastoparan X, and HR1-from solitary wasp venom exhibit potent anticancer activity toward human glioblastoma multiforme cells. Importantly, the antiglioblastoma action of mastoparan peptides occurs by membranolytic activity, leading to necrosis. Our data also suggest a direct relation between mastoparan membranolytic potency and the presence of negatively charged phospholipids like phosphatidylserine. Collectively, these data may warrant additional studies for mastoparan peptides as new agents for the treatment of glioblastoma multiforme brain tumor.

Paper title : Novel mode of action of polybia-MPI, a novel antimicrobial peptide, in multi-drug resistant leukemic cells.

Doi : https://doi.org/10.1016/j.canlet.2008.12.027

Abstract : As the frequent emergency of resistant tumor cells during treatment, the development of new agents with new modes of action attracts a great deal of interest. Polybia-MPI was a short cationic alpha-helical amphiphilic peptide that has selective toxicity toward cancer cells but no hemolytic activity. Its target selectivity is based on the binding preference to membranes containing anionic phospholipids by electrostatic driving. Its ability to make PI and trypan blue permeate into tumor cells at the same rate (within minutes), suggests a killing mechanism that involves plasma membrane perturbation. SEM and confocal microscopy experiments verified that the cell died as a result of acute injury and bursting, suggesting necrosis. As compared to the conventional chemotherapy, polybia-MPI targets at the cell membrane rather than enters into the cell to exert its action. So it is difficult for tumor cells to develop resistance to polybia-MPI during treatment and its action is not affected by the common multi-drug resistant mechanism. Although this is an initial study that looked at its in vitro activity rather than the in vivo activity, with the increasing resistance of conventional chemotherapy, polybia-MPI may offer a novel therapeutic strategy in the treatment of multi-drug resistant cancer.

Paper title : Influence of the bilayer composition on the binding and membrane disrupting effect of Polybia-MP1, an antimicrobial mastoparan peptide with leukemic T-lymphocyte cell selectivity.

Doi : https://doi.org/10.1021/bi201608d

Abstract : This study shows that MP-1, a peptide from the venom of the Polybia paulista wasp, is more toxic to human leukemic T-lymphocytes than to human primary lymphocytes. By using model membranes and electrophysiology measurements to investigate the molecular mechanisms underlying this selective action, the porelike activity of MP-1 was identified with several bilayer compositions. The highest average conductance was found in bilayers formed by phosphatidylcholine or a mixture of phosphatidylcholine and phosphatidylserine (70:30). The presence of cholesterol or cardiolipin substantially decreases the MP-1 pore activity, suggesting that the membrane fluidity influences the mechanism of selective toxicity. The determination of partition coefficients from the anisotropy of Trp indicated higher coefficients for the anionic bilayers. The partition coefficients were found to be 1 order of magnitude smaller when the bilayers contain cholesterol or a mixture of cholesterol and sphingomyelin. The blue shift fluorescence, anisotropy values, and Stern-Volmer constants are indications of a deeper penetration of MP-1 into anionic bilayers than into zwitterionic bilayers. Our results indicate that MP-1 prefers to target leukemic cell membranes, and its toxicity is probably related to the induction of necrosis and not to DNA fragmentation. This mode of action can be interpreted considering a number of bilayer properties like fluidity, lipid charge, and domain formation. Cholesterol-containing bilayers are less fluid and less charged and have a tendency to form domains. In comparison to healthy cells, leukemic T-lymphocyte membranes are deprived of this lipid, resulting in decreased peptide binding and lower conductance. We showed that the higher content of anionic lipids increases the level of binding of the peptide to bilayers. Additionally, the absence of cholesterol resulted in enhanced pore activity. These findings may drive the selective toxicity of MP-1 to Jurkat cells.