Anticancer activity of VmCT1 analogs against MCF‐7 cells

Abstract

Antimicrobial peptides are considered promising drug candidates due to their broad range of activity. VmCT1 (Phe-Leu-Gly-Ala-Leu-Trp-Asn-Val-Ala-Lys-Ser-Val-Phe-NH ) is an α-helical antimicrobial peptide that was obtained from the Vaejovis mexicanus smithi scorpion venom. Some of its analogs showed to be as antimicrobial as the wild type, and they were designed for understanding the influence of physiochemical parameters on antimicrobial and hemolytic activity. Some cationic antimicrobial peptides exhibit anticancer activity so VmCT1 analogs were tested to verify the anticancer activity of this family of peptides. The analogs were synthesized, purified, characterized, and the conformational studies were performed. The anticancer activity was assessed against MCF-7 mammary cancer cells. The results indicated that [Glu] -VmCT1-NH , [Lys] -VmCT1-NH , and [Lys] -VmCT1-NH analogs presented moderated helical tendency (0.23-0.61) and tendency of anticancer activity at 25 μmol/L in 24 hr of experiment; and [Trp] -VmCT1-NH analog that presented low helical tendency and moderated anticancer activity at 50 μmol/L. These results demonstrated that single substitutions on VmCT1 led to different physicochemical features and could assist on the understanding of anticancer activity of this peptide family.

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

“…The peptides tested in this study presented intermediary activity when compared to other AMPs families. Pol-CP-NH 2 was more active against the cancer cell lines used in this study than VmCT1 and analogs 18 but it was not as active as decoralin and its derivatives. 17 Here, we identify novel and previously undisclosed antiplasmodial and anticancer properties for a class of wasp venom-derived peptides and use a physicochemical feature-guided design approach to identify relevant functional determinants.…”

“…For example, recent reports have described the design of AMPs with broad‐spectrum activity, particularly amphipathic cationic peptides 11 . Exploring the multifunctional properties of these molecules may lead to candidate molecules that simultaneously kill resistant microorganisms, viruses, 12 parasite infections, 13‐16 and cancer cells 17,18 …”

“…11 Exploring the multifunctional properties of these molecules may lead to candidate molecules that simultaneously kill resistant microorganisms, viruses, 12 parasite infections, [13][14][15][16] and cancer cells. 17,18 Torres et al 6 using a physicochemical feature-guided design of polybia-CP (Pol-CP-NH 2 : Ile-Leu-Gly-Thr-Ile-Leu-Gly-Leu-Leu-Lys-Ser-Leu-NH 2 ), identified functional determinants that were key for converting a toxic wasp venom peptide into nontoxic variants with enhanced antimicrobial activity against fungi, Gram-positive and Gram-negative bacteria by destabilizing the membrane of those microorganisms. The structure-guided design of active derivatives of Pol-CP-NH 2 involved reprogramming peptide features to favor the interaction between AMPs and negatively charged biomembranes.…”

“…(a) The importance of physicochemical properties required for antiplasmodial activity exhibited in (b) the heat map containing fluorescent sporozoites (membrane disrupted, shown in blue) in the presence of increasing concentration of the peptides.In red, we highlight the conditions at which the peptides were not active against the Plasmodium sporozoites. Experiments were performed in three independent replicates with three repetitions for each condition membrane morphology and composition,33,34 compared to the healthy mammalian cells, however they all have an abnormal net negative charge35 (Figure 3a), because of the overexpression of anionic molecules such as phosphatidylserines, glycoproteins, and glycosaminoglycans,18 which we reasoned would interact with our peptides electrostatically.The inhibitory activities observed against cancer cell lines are at the same range of concentrations reported for antimicrobial activityFigure 2b) for this family of peptides. The model molecule, Pol-CP-NH 2 , exhibited the highest anticancer activity among all tested peptides (Figure 3bandSupplementary Table 2).…”

Reprogramming biological peptides to combat infectious diseases

“…However, AMPs can also be repurposed to target other types of cells such as pathogenic microorganisms (e.g., protozoa), [103][104][105][106][107][108][109][110] or cancer cells. 43,111 Decoralin, a broad-spectrum antibacterial AMP from the venom of the wasp Oreumenes decoratum, was recently reported to be inactive against Plasmodium species. However, by modifying the N-terminal extremity of this cytotoxic peptide, we were able to create synthetic derivatives having antiplasmodial activity at sub-micromolar concentrations that were not toxic against mammalian cells.…”