Recently, the dramatic emergence of antimicrobial resistance has received attention from World Health Organization. Synthetic antimicrobial peptides (SAMPs) are considered new weapons to fight ...against infections caused by multi-drug resistant pathogens. Here, the authors provide an overview of the current research on SAMPs. The focus is SAMPs, how to design them, which features must be considered during design, and comparison with natural peptides. This review also includes a discussion about the natural AMPs, mechanisms of action and applications as new drugs or even as adjuvants molecules to enhance commercial drugs activity. The advances in chemical synthesis have reduced the cost to produce synthetic peptides open ways to achieve new antimicrobial agents. Therefore, synthetic peptides are new promising molecules to safeguard human and animal health.
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Laticifers have been utilized as paradigms to enhance comprehension of specific facets of plant ecology and evolution. From the beginning of seedling growth, autonomous laticifer networks are formed ...throughout the plant structure, extending across all tissues and organs. The vast majority of identified products resulting from laticifer chemistry and metabolism are linked to plant defense. The latex, which is the fluid contained within laticifers, is maintained under pressure and has evolved to serve as a defense mechanism against both aggressors and invaders, irrespective of their capabilities or tactics. Remarkably, the latex composition varies among different species. The current goal is to understand the specific functions of various latex components in combating plant enemies. Therefore, the study of latex's chemical composition and proteome plays a critical role in advancing our understanding about plant defense mechanisms. Here, we will discuss some of these aspects.
•Latex is constitutively present in all green parts of laticifer plants.•Latex-bearing plants have been studied as models for understanding plant defense.•The chemical composition of each latex fluid is unique.•Peptidases and chitinases are the most common constitutive proteins in latex.•Latex fluids also contain different types of toxic secondary metabolites.
Antimicrobial peptides, also known as AMPs, are cationic and amphipathic molecules found in all living organisms, composing part of the defense mechanisms against various pathogens, including fungi, ...viruses, bacteria, and nematodes. AMPs derived from plants are the focus of this review because they have gained attention as alternative molecules to overcome pathogen resistance as well as new drugs to combat cancer. Plant AMPs are generally classified based on their sequences and structures, as thionins, defensins, hevein-like peptides, knottins, stable-like peptides, lipid transfer proteins, snakins, and cyclotides. Although there are studies reporting the toxicity of plant AMPs to nontarget cells or limitations of oral administration, synthetic AMPs with reduced toxicity or allergenicity, or greater resistance to peptidases can be designed by using different bioinformatics tools. Thus, this review provides information about the classification of plant AMPs, their characteristics, mechanisms of action, hemolytic and cytotoxic potential, possible applications in the medical field, and finally, the use of bioinformatics to help design synthetic AMPs with improved features.
The way how to obtain peptides from plants and evaluate their antimicrobial activity and toxicity. Display omitted
•Antimicrobial peptides were generated from the hydrolysis of wheat gluten proteins.•The hydrolysates exhibited activity against the all six tested fungi.•The hydrolysates extended the shelf life of ...bread in three days.•28 peptides were sequenced and then the best four peptides were synthesized.•The peptides were able to induce damage to the fungal plasma membrane.
Antimicrobial peptides (AMPs) have been reported to be promising alternatives to chemical preservatives. Thus, this study aimed to characterise AMPs generated from the hydrolysis of wheat gluten proteins using latex peptidases of Calotropis procera, Cryptostegia grandiflora, and Carica papaya. The three hydrolysates (obtained after 16 h at 37 °C, using a 1: 25 enzyme: substrate ratio) inhibited the growth of Aspergillus niger, A. chevalieri, Trichoderma reesei, Pythium oligandrum, Penicillium sp., and Lasiodiplodia sp. by 60–90%, and delayed fungal growth on bread by 3 days when used at 0.3 g/kg. Moreover, the specific volume and expansion factor of bread were not affected by the hydrolysates. Of 28 peptides identified, four were synthesised and exhibited activity against Penicillium sp. Fluorescence and scanning electron microscopy suggested that the peptides damaged the fungal plasma membrane. Bioinformatics analysis showed that no peptide was toxic and that the antigenic ones had cleavage sites for trypsin or pepsin.
The global outbreak of COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome caused by Coronavirus 2) began in December 2019. Its closest relative, SARS-CoV-1, ...has a slightly mutated Spike (S) protein, which interacts with ACE2 receptor in human cells to start the infection. So far, there are no vaccines or drugs to treat COVID-19. So, research groups worldwide are seeking new molecules targeting the S protein to prevent infection by SARS-CoV-2 and COVID-19 establishment. We performed molecular docking analysis of eight synthetic peptides against SARS-CoV-2 S protein. All interacted with the protein, but Mo-CBP3-PepII and PepKAA had the highest affinity with it. By binding to the S protein, both peptides led to conformational alterations in the protein, resulting in incorrect interaction with ACE2. Therefore, given the importance of the S protein-ACE2 interaction for SARS-CoV-2 infection, synthetic peptides could block SARS-CoV-2 infection. Moreover, unlike other antiviral drugs, peptides have no toxicity to human cells. Thus, these peptides are potential molecules to be tested against SARS-CoV-2 and to develop new drugs to treat COVID-19.
•Synthetic peptides bind to SARS-CoV-2 Spike protein.•Synthetic peptides induced conformational changes on SARS-CoV-2 spike protein structure.•Synthetic peptides bind to ACE2 protein but did not affect its structure.•Synthetic peptides induced the wrong interaction of SARS-CoV-2 with ACE2 receptor.
•Calotropis procera cysteine peptidases (CpCPs) were immobilized on glyoxyl-agarose.•Casein hydrolysis by glyoxyl-CpCPs was similar to soluble form and chymosin.•The casein micelle aggregation also ...was very similar to soluble form and chymosin.•Glyoxyl-CpCPs performed well after five reaction cycles.•Glyoxyl-CpCPs produced cheeses with characteristics similar to those using chymosin.
Calotropis procera cysteine peptidases (CpCPs) have presented several potential biotechnological applications. Here, these enzymes were immobilized on glyoxyl-agarose (glyoxyl-CpCPs) with yields of 90–95 % and the recovered activities ranged from 10 % to 15 %, according to enzyme loadings (5, 10, 20, 40, and 50 mgBSAeq/g). Spectrophotometric assays and SDS-PAGE showed that the casein hydrolysis by glyoxyl-CpCPs was similar to soluble CpCPs. In addition, glyoxyl-CpCPs exhibited similar ratio of milk-clotting activity to proteolytic activity in comparison with soluble CpCPs and chymosin. Even after being stored for six months at 8 °C, the residual proteolytic activity of glyoxyl-CpCPs remained close to 100 %. Atomic force microscopy and dynamic light scattering techniques showed that the process of casein micelle aggregation after treatment with glyoxyl-CpCPs was very similar to its soluble form and chymosin. Glyoxyl-CpCPs performed well after five reaction cycles, producing cheeses with yield, moisture, protein, and fat similar to those produced with chymosin.
The emergence of antibiotic-resistant microbes has stimulated research worldwide seeking new biologically active molecules. In this respect, synthetic antimicrobial peptides (SAMPs) have been ...suggested to overcome this problem. Although there are some online servers that provide putative SAMPs from protein sequences, the choice of the best peptide sequences for further analysis is still difficult. Therefore, the goal of this paper is not to launch a new tool but to provide a friendly workflow to characterize and predict potential SAMPs by employing existing tools. Using this proposed workflow, two peptides (PepGAT and PepKAA) were obtained and extensively characterized. These peptides damaged microbial membranes and cell walls, and induced overproduction of reactive oxygen species (ROS). Both peptides were found to assume random coil secondary structure in aqueous solution, organic solvent, and upon binding to negatively charged lipid systems. Peptides were also able to degrade formed biofilms but not to prevent biofilm formation. PepGAT was not resistant to proteolysis, whereas PepKAA was resistant to pepsin but not to pancreatin. Furthermore, both presented no hemolytic activity against red blood cells, even at a 10-fold higher concentration than the antimicrobial concentration. The pipeline proposed here is an easy way to design new SAMPs for application as alternatives to develop new drugs against human pathogenic microorganisms.
•Here is provided a workflow to facilitate the design of synthetic peptides.•Employing the workflow was possible to design two antimicrobial peptides.•PepGAT and PepKAA are potent antimicrobial peptides.•Both peptides have activity against human pathogenic bacteria and fungi.
•Latex peptidases were able to perform total hydrolysis of caseins.•On the other hand, whey proteins were more resistant to proteolysis.•Heat pretreatment of the whey proteins enhanced the degree of ...hydrolysis.•In vivo tests showed that latex peptidases reduced antigenicity and allergenicity.•Results were similar to a commercial partially hydrolyzed formula.
The present study evaluated four laticifer fluids as a novel source of peptidases capable of hydrolyzing proteins in cow’s milk. The latex peptidases from Calotropis procera (CpLP), Cryptostegia grandiflora (CgLP), and Carica papaya (CapLP) were able to perform total hydrolysis of caseins after 30 min at pH 6.5, as confirmed by a significant reduction in the residual antigenicity. Casein hydrolysis by Plumeria rubra latex peptidases (PrLP) was negligible. Moreover, whey proteins were more resistant to proteolysis by latex peptidases; however, heat pretreatment of the whey proteins enhanced the degree of hydrolysis and reduced the residual antigenicity of the hydrolysates. The in vivo assays show that the cow’s milk proteins hydrolysed by CgLP and CapLP exhibited no immune reactions in mice allergic to cow’s milk, similar to a commercial partially hydrolysed formula. Thus, these peptidases are promising enzymes for the development of novel hypoallergenic formulas for children with a milk allergy.
According to the WHO, 20–25% of people worldwide are affected by skin infections caused by dermatophytes, such as those of the Trichophyton genus. Additionally, several dermatophytes have developed ...resistance to drugs such as griseofulvin and itraconazole. This study tested 2S albumins-derived antimicrobial peptides (AMPs) as alternative antidermatophytic molecules.
Membrane pore formation assays, tests to detect overproduction of ROS, scanning electron microscopy (SEM) and fluorescence microscopy (FM) were carried out to provide insight into the mechanisms of antidermatophytic action.
All AMPs (at 50 μg mL−1) tested reduced the mycelial growth of T. mentagrophytes and T. rubrum by up to 95%. In contrast, using a concentration 20-fold higher, griseofulvin only inhibited T. mentagrophytes by 35%, while itraconazole was not active against both dermatophytes. Scanning electron and fluorescence microscopies revealed that the six AMPs caused severe damage to hyphal morphology by inducing cell wall rupture, hyphal content leakage, and death. Peptides also induced membrane pore formation and oxidative stress by overproduction of ROS. Based on the stronger activity of peptides than the commercial drugs and the mechanism of action, all six peptides have the potential to be either employed as models to develop new antidermatophytic drugs or as adjuvants to existing ones.
The synthetic peptides are more efficient than conventional drug to treat infection caused by dermatophytes being potential molecules to develop new drugs.
•All synthetic peptides tested reduced the mycelial growth of Trichophyton mentagrophytes and T. rubrum.•The synthetic peptides induced severe morphological damage in dermatophytes hyphae.•The synthetic peptides induced membrane pore formation and ROS overproduction in fungal hyphae•The synthetic peptides were more effective than the commercial drugs Griseofulvin and Itraconazole
Vigna unguiculata is an important source of proteins and energy for humans and animals. However, postharvest losses caused by Callosobruchus maculatus can reach from 20 to 100% of stored seeds. In ...this study, the insecticide potential of compounds extracted from Himatanthus drasticus latex was assessed. The latex was extracted with ethanol (70%) and then partitioned through sequential use of hexane and chloroform. These fractions were investigated by chromatography to determine their chemical composition. Plumieride, identified in a hydroalcoholic subfraction, was tested for insecticidal activity against C. maculatus. The ethanolic fraction (LC50 = 0.109; LC90 = 0.106%) and the plumieride (LC50 = 0.166; LC90 = 0.167%) were lethal to larvae. Plumieride (0.25%) delayed larval development, and mortality reached 100%. Its inhibitory action on intestinal α-amylase from larvae was higher (89.12%) than that of acarbose (63.82%). Plumieride (0.1%) inhibited the enzyme α-amylase in vivo in the larval intestine. This result was confirmed by a zymogram test performed by SDS-PAGE when the enzyme electrophoresed on gel copolymerized with starch. When spread on seeds, the hydroalcoholic fraction (1.0%) reduced infestation. The loss of seed mass was 5.26% compared to the control (44.97%). The results confirm the effect of latex compounds in protecting stored seeds against weevil infestation.
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