Peptide name : Amphipathic peptide VmCT1

Source/Organism : Scorpions, Morelos, located in South-Central Mexico (Mexican scorpion)

Linear/Cyclic : Not found

Chirality : Not found

Peptide length: 68

C-terminal modification: Not found

N-terminal modification : Amidation

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : Not found

Cell line : Not found

Cancer type : Not found

Other activity : Anti-bacterial activity; Anti-microbial activity; Anti-malarial activitiy

Amino acid composition bar chart :

Molecular mass : 7769.9438 Dalton

Aliphatic index : 1.189

Instability index : 49.6912

Hydrophobicity (GRAVY) : 0.2456

Isoelectric point : 4.832

Charge (pH 7) : -3.3995

Aromaticity : 0.102

Molar extinction coefficient (cysteine, cystine): (6990, 6990)

Hydrophobic/hydrophilic ratio : 1.26666666

hydrophobic moment : 0.0293

Missing amino acid : C

Most occurring amino acid : L

Most occurring amino acid frequency : 12

Least occurring amino acid : H

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.4, 0.2, 0.4)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCSC)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)[C@@H](C)O)C(C)C)C(C)C

1 : Pedron CN, et al. Repurposing the scorpion venom peptide VmCT1 into an active peptide against Gram-negative ESKAPE pathogens. Bioorg Chem. 2019; 90:103038. doi: 10.1016/j.bioorg.2019.103038

2 : Pedron CN, et al. Net charge tuning modulates the antiplasmodial and anticancer properties of peptides derived from scorpion venom. J Pept Sci. 2021; 27:e3296. doi: 10.1002/psc.3296

3 : Zeng XC, et al. Three new antimicrobial peptides from the scorpion Pandinus imperator. Peptides. 2013; 45:28-34. doi: 10.1016/j.peptides.2013.03.026

4 : Pedron CN, et al. The effect of lysine substitutions in the biological activities of the scorpion venom peptide VmCT1. Eur J Pharm Sci. 2019; 136:104952. doi: 10.1016/j.ejps.2019.06.006

5 : Pedron CN, et al. Novel designed VmCT1 analogs with increased antimicrobial activity. Eur J Med Chem. 2017; 126:456-463. doi: 10.1016/j.ejmech.2016.11.040

6 : Pedron CN, et al. Arg-substituted VmCT1 analogs reveals promising candidate for the development of new antichagasic agent. Parasitology. 2020; 147:1810-1818. doi: 10.1017/S0031182020001882

7 : Ramírez-Carreto S, et al. Gene cloning and functional characterization of four novel antimicrobial-like peptides from scorpions of the family Vaejovidae. Peptides. 2012; 34:290-5. doi: 10.1016/j.peptides.2012.02.002

8 : Almaaytah A and Albalas Q. Scorpion venom peptides with no disulfide bridges: a review. Peptides. 2014; 51:35-45. doi: 10.1016/j.peptides.2013.10.021

Paper title : Repurposing the scorpion venom peptide VmCT1 into an active peptide against Gram-negative ESKAPE pathogens.

Doi : https://doi.org/10.1016/j.bioorg.2019.103038

Abstract : VmCT1 is a cationic antimicrobial peptide (AMP) from the venom of the scorpion Vaejovis mexicanus. VmCT1 and analogs were designed with single substitutions for verifying the influence of changes in physicochemical features described as important for AMPs antimicrobial and hemolytic activities, as well as their effect on VmCT1 analogs resistance against proteases action. The increase of the net positive charge by the introduction of an arginine residue in positions of the hydrophilic face of the helical structure affected directly the antimicrobial activity. Arg-substituted analogs presented activity against Gram-negative bacteria from the ESKAPE list of pathogens that were not observed for VmCT1. Additionally, peptides with higher net positive charge presented increased antimicrobial activity with values ranging from 0.39 to 12.5 μmol L-1 against Gram-positive and Gram-negative bacteria and fungi. The phenylalanine substitution by glycine (position 1), and the valine substitution by a proline residue (position 8) led to analogs with lower hemolytic activity (at concentrations 50 and 100 μmol L-1, respectively). These results revealed that it is possible to modulate the biological activities of VmCT1 derivatives by designing single substituted-analogs as prospective therapeutics against bacteria and fungi.

Paper title : Net charge tuning modulates the antiplasmodial and anticancer properties of peptides derived from scorpion venom.

Doi : https://doi.org/10.1002/psc.3296

Abstract : VmCT1, a linear helical antimicrobial peptide isolated from the venom of the scorpion Vaejovis mexicanus, displays broad spectrum antimicrobial activity against bacteria, fungi, and protozoa. Analogs derived from this peptide containing single Arg-substitutions have been shown to increase antimicrobial and antiparasitic activities against Trypanossoma cruzi. Here, we tested these analogs against malaria, an infectious disease caused by Plasmodium protozoa, and assessed their antitumoral properties. Specifically, we tested VmCT1 synthetic variants [Arg]3 -VmCT1-NH₂ , [Arg]7 -VmCT1-NH₂ , and [Arg]11 -VmCT1-NH₂ , against Plasmodium gallinaceum sporozoites and MCF-7 mammary cancer cells. Our screen identified peptides [Arg]3 -VmCT1-NH₂ and [Arg]7 -VmCT1-NH₂ as potent antiplasmodial agents (IC₅₀ of 0.57 and 0.51 μmol L-1 , respectively), whereas [Arg]11 -VmCT1-NH₂ did not show activity against P. gallinaceum sporozoites. Interestingly, all peptides presented activity against MCF-7 and displayed lower cytotoxicity toward healthy cells. We demonstrate that increasing the net positive charge of VmCT1, through arginine substitutions, modulates the biological properties of this peptide family yielding novel antiplasmodial and antitumoral molecules.

Paper title : Three new antimicrobial peptides from the scorpion Pandinus imperator.

Doi : https://doi.org/10.1016/j.peptides.2013.03.026

Abstract : Three novel cysteine-free venom peptides, which were referred to as Pantinin-1, Pantinin-2 and Pantinin-3, respectively, have been identified from the scorpion Pandinus imperator by cDNA cloning strategy. The precursor of each peptide consists of a signal peptide, a mature peptide with no disulfide bridges, and an acidic propeptide with a typical processing signal. Each of the three peptides is an α-helical, cationic and amphipathic molecule with 13 or 14 amino acid residues. Their amino acid sequences are homologous to those of some 13-mer antimicrobial peptides isolated from scorpions. Antimicrobial assay showed that all the three peptides possess relatively strong activities against Gram-positive bacteria and a fungus, but have very weak antimicrobial activities against Gram-negative bacteria. Toxicity assay showed that the three peptides exhibit very low or mild hemolytic activities against human red blood cells. It is interesting to see that Pantinin-3 is able to potently inhibit the growth of vancomycin-resistant Enterococcus (VRE) S13, a pathogen that can cause a number of human infections; this suggests that Pantinin-3 has great potential to be applied in the treatment of VRE infections. Our findings gain new insights into the structure/function relationships of the small linear cationic antimicrobial peptides from scorpions, and provide new templates for designing of antimicrobial agents targeting antibiotic-resistant pathogenic bacteria.

Paper title : The effect of lysine substitutions in the biological activities of the scorpion venom peptide VmCT1.

Doi : https://doi.org/10.1016/j.ejps.2019.06.006

Abstract : Antimicrobial peptides (AMPs) are biologically active molecules with a broad-spectrum activity against a myriad of microorganisms. Aside from their antimicrobial functions, AMPs present physicochemical and structural properties that allow them to exert activity against other kind of cells, such as cancer cells. VmCT1 is a potent cationic amphipathic AMP from the venom of the scorpion Vaejovis mexicanus. In this study, we designed lysine-substituted VmCT1 analogs for verifying the influence of changes in the net positive charge on biological activities. The increase in the net positive charge caused by lysine substitutions in the hydrophilic portion, led to higher antimicrobial activity values (0.1-6.3 μmol L-1) than VmCT1 (0.8-50 μmol L-1) and higher activity against mammary cancer cells MCF-7 (6.3-12.5 μmol L-1) than VmCT1 (12.5 μmol L-1). Contrarily, when lysine-substitutions were made at the hydrophobic portion of the helical projection, the activity values decreased. However, the lysine-substitution at the center of the hydrophobic face led to the generation of an analog with antiplasmodial activity at the same concentration presented by VmCT1 (0.8 μmol L-1). In this study, we demonstrated that it is possible to modulate biological activities and cytotoxicity of VmCT1 peptides by increasing their net positive charge using lysine residues, thus creating alternatives for standard-of-care therapeutics against different types of microorganisms and MCF-7 human breast cancer cells.

Paper title : Novel designed VmCT1 analogs with increased antimicrobial activity.

Doi : https://doi.org/10.1016/j.ejmech.2016.11.040

Abstract : Antimicrobial peptides are biologically active molecules produced by a wide range of organisms as an essential component of the innate immune response. They have recently attracted great interest, since they have antimicrobial activity against a broad spectrum of microorganisms. VmCT1 is a cationic peptide from the venom of Vaejovis mexicanus smithi scorpions, which presents antibacterial activity and tends to helical structures. Its analogs were synthesized, characterized and the conformational studies were performed by circular dichroism. The peptides were designed to verify if the single and double substitutions proposed at the hydrophilic and hydrophobic portions of the amphipathic structure would alter antimicrobial activity against Gram-negative and Gram-positive bacteria, yeast and filamentous fungus, besides the hemolytic activity in human erythrocytes. Total charge of the peptides were modified from +2 to +3 by the introduction of a Lysine residue in the hydrophilic face of the amphiphilic helical structure leading to enhanced antimicrobial activity. [K]11-VmCT1-NH₂ presented the lower MIC value against the microorganisms (from 0.39 to 6.25 μmol L-1), however it showed higher hemolytic activity. The other Lysine-substituted analogs presented also lower MIC values ranging from 0.39 to 25 μmol L-1 for the microorganisms assessed. The circular dichroism spectra analyses suggest that the Lysine-substituted analogs tend to adopt helical structures in trifluoroethanol solution and vesicles (f_H: 0.43-1), however they were coiled in water. Alanine substitution by a Glutamic acid residue in the hydrophilic face promotes the increase of polar angle in [E]4-VmCT1-NH₂ analog, which was important to led lower hemolytic activity (MHC value = 25 μmol L-1). [W]9-VmCT1-NH₂ and [E]4[W]9-VmCT1-NH₂ were designed to favors hydrophobic interactions by the introduction of Tryptophan residue. [W]9-VmCT1-NH₂ presented MIC values lower or similar than the model molecule in the most of microorganisms tested. These results provided information about the structure-activity relationship and showed the influence of physicochemical parameters on antimicrobial and hemolytic activity.

Paper title : Arg-substituted VmCT1 analogs reveals promising candidate for the development of new antichagasic agent.

Doi : https://doi.org/10.1017/S0031182020001882

Abstract : VmCT1 is an antimicrobial peptide (AMP) isolated from the venom of the scorpion Vaejovis mexicanus with antimicrobial, anticancer and antimalarial activities, which the rational design with Arg-substitution has yielded AMPs with higher antimicrobial activity than VmCT1. Chagas is a neglected tropical disease, becoming the development of new antichagasic agents is urgent. Thus, we aimed to evaluate the antichagasic effect of VmCT1 and three Arg-substituted analogues, as well their action mechanism. Peptides were tested against the epimastigote, trypomastigote, amastigote forms of Trypanossoma cruzi Y strain and against LLC-MK2 mammalian cells. The mechanism of action of these peptides was evaluated by means of flow cytometry and scanning electron microscopy. VmCT1 presented activity against all three forms of T. cruzi, with EC50 against trypomastigote forms of 1.37 μmol L-1 and selectivity index (SI) of 58. [Arg]3-VmCT1, [Arg]7-VmCT1 and [Arg]11-VmCT1 also showed trypanocidal effect, but [Arg]11-VmCT1 had the best effect, being able to decrease the EC50 against trypomastigote forms to 0.8 μmol L-1 and increase SI to 175. Necrosis was cell death pathway of VmCT1, as well [Arg]7-VmCT1 and [Arg]11-VmCT1, such as observed by membrane damage in flow cytometry analyses and scanning-electron-microscopy. In conclusion, [Arg]11-VmCT1 revealed promising as a candidate for new antichagasic therapeutics.

Paper title : Gene cloning and functional characterization of four novel antimicrobial-like peptides from scorpions of the family Vaejovidae.

Doi : https://doi.org/10.1016/j.peptides.2012.02.002

Abstract : From the cDNA libraries made from the venom glands of two scorpions belonging to the Vaejovidae family, four different putative non disulfide-bridged antimicrobial peptides were identified: VmCT1 and VmCT2 from Vaejovis mexicanus smithi plus VsCT1 and VsCT2 from Vaejovis subcristatus. These short peptides (with only 13 amino acid residues each) share important amino acid sequence similarities among themselves and with other reported antimicrobial peptides, but their biological activities vary dramatically. This communication reports the cloning, chemical synthesis and characterization of these peptides. Two peptides, VmCT1 and VmCT2 showed broad-spectrum antibacterial activity with minimum inhibitory concentrations MICs in the range of 5-25 μM and 10-20 μM respectively, whereas their hemolytic activity at these concentrations was low. Structure-function relationships that might determine the differences in activities are discussed.

Paper title : Scorpion venom peptides with no disulfide bridges: a review.

Doi : https://doi.org/10.1016/j.peptides.2013.10.021

Abstract : Scorpion venoms are rich sources of biologically active peptides that are classified into disulfide-bridged peptides (DBPs) and non-disulfide-bridged peptides (NDBPs). DBPs are the main scorpion venom components responsible for the neurotoxic effects observed during scorpion envenomation as they usually target membrane bound ion channels of excitable and non-excitable cells. Several hundred DBPs have been identified and functionally characterized in the past two decades. The NDBPs represent a novel group of molecules that have gained great interest only recently due to their high diversity both in their primary structures and bioactivities. This review provides an overview of scorpion NDBPs focusing on their therapeutic applications, modes of discovery, mechanisms of NDBPs genetic diversity and structural properties. It also provides a simple classification for NDBPs that could be adopted and applied to other NDBPs identified in future studies.