Anti-Staphy Peptides Rationally Designed from Cry10Aa Bacterial Protein.

Bacterial infections pose a significant threat to human health, constituting a major challenge for healthcare systems. Antibiotic resistance is particularly concerning in the context of treating staphylococcal infections. In addressing this challenge, antimicrobial peptides (AMPs), characterized by their hydrophobic and cationic properties, unique mechanism of action, and remarkable bactericidal and immunomodulatory capabilities, emerge as promising alternatives to conventional antibiotics for tackling bacterial multidrug resistance. This study focuses on the Cry10Aa protein as a template for generating AMPs due to its membrane-penetrating ability. Leveraging the Joker algorithm, six peptide variants were derived from α-helix 3 of Cry10Aa, known for its interaction with lipid bilayers. In vitro, antimicrobial assays determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) required for inhibiting the growth of Staphylococcus aureus, Escherichia coli, Acinetobacter baummanii, Enterobacter cloacae, Enterococcus facallis, Klebsiella pneumonia, and Pseudomonas aeruginosa. Time-kill kinetics were performed using the parental peptide AMPCry10Aa, as well as AMPCry10Aa_1 and AMPCry10Aa_5, against E. coli ATCC, S. aureus 111 and S. aureus ATCC strains showing that AMPCry10Aa_1 and AMPCry10Aa_5 peptides can completely reduce the initial bacterial load with less than 2 h of incubation. AMPCry10Aa_1 and AMPCry 10Aa_5 present stability in human serum and activity maintenance up to 37 °C. Cytotoxicity assays, conducted using the MTT method, revealed that all of the tested peptides exhibited cell viability >50% (IC50). The study also encompassed evaluations of the structure and physical-chemical properties. The three-dimensional structures of AMPCry10Aa and AMPCry10Aa_5 were determined through nuclear magnetic resonance (NMR) spectroscopy, indicating the adoption of α-helical segments. Electron paramagnetic resonance (EPR) spectroscopy elucidated the mechanism of action, demonstrating that AMPCry10Aa_5 enters the outer membranes of E. coli and S. aureus, causing substantial increases in lipid fluidity, while AMPCry10Aa slightly increases lipid fluidity in E. coli. In conclusion, the results obtained underscore the potential of Cry10Aa as a source for developing antimicrobial peptides as alternatives to conventional antibiotics, offering a promising avenue in the battle against antibiotic resistance.

Antiviral Activities of Mastoparan-L-Derived Peptides against Human Alphaherpesvirus 1.

Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective against HSV-1. This study aimed to demonstrate the antiviral properties of mastoparans, including mastoparan-L [I5, R8], mastoparan-MO, and [I5, R8] mastoparan, against HSV-1. Initially, Vero cell viability was assessed in the presence of these peptides, followed by the determination of antiviral activity, mechanism of action, and dose-response curves through plaque assays. Structural analyses via circular dichroism and nuclear magnetic resonance were conducted, along with evaluating membrane fluidity changes induced by [I5, R8] mastoparan using fluorescence-labeled lipid vesicles. Cytotoxic assays revealed high cell viability (>80%) at concentrations of 200 µg/mL for mastoparan-L and mastoparan-MO and 50 µg/mL for [I5, R8] mastoparan. Mastoparan-MO and [I5, R8] mastoparan exhibited over 80% HSV-1 inhibition, with up to 99% viral replication inhibition, particularly in the early infection stages. Structural analysis indicated an α-helical structure for [I5, R8] mastoparan, suggesting effective viral particle disruption before cell attachment. Mastoparans present promising prospects for HSV-1 infection control, although further investigation into their mechanisms is warranted.

A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models.

In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds. To evaluate the antioxidant and neuroprotective activities of the arylpiperazine derivatives, we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (neurotoxicity induced by 3-nitropropionic acid in Swiss mice) models. In the in vitro tests, LQFM181 showed the most promising antioxidant activity at the neuronal membrane and cytoplasmic levels, and significant neuroprotective activity against the neurotoxicity induced by 3-nitropropionic acid. Hence, this compound was further subjected to in vivo evaluation, which demonstrated remarkable antioxidant capacity such as reduction of MDA and carbonyl protein levels, increased activities of succinate dehydrogenase, catalase, and superoxide dismutase. Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection.

Chrysin bonded to ß-d-glucose tetraacetate enhances its protective effects against the neurotoxicity induced by aluminum in Swiss mice.

OBJECTIVES: To evaluate whether the glycosylation of chrysin (CHR) enhances its protective effects against aluminum-induced neurotoxicity. METHODS: To compare the antioxidant, anticholinesterase, and behavioral effects of CHR with its glycosylated form (CHR bonded to ß-d-glucose tetraacetate, denoted as LQFM280), we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (aluminum-induced neurotoxicity in Swiss mice) models. KEY FINDINGS: LQFM280 demonstrated higher antioxidant activity than CHR in both models. Specifically, LQFM280 exhibited the ability to exert antioxidant effects in the cytoplasm of SH-SY5Y cells, indicating its competence in traversing neuronal membranes. Remarkably, LQFM280 proved more effective than CHR in recovering memory loss and counteracting neuronal death in the aluminum chloride mice model, suggesting its increased bioavailability at the brain level. CONCLUSIONS: The glycosylation of CHR with ß-d-glucose tetraacetate amplifies its neuroprotective effects, positioning LQFM280 as a promising lead compound for safeguarding against neurodegenerative processes involving oxidative stress.

Novel Proline Transporter Inhibitor (LQFM215) Presents Antipsychotic Effect in Ketamine Model of Schizophrenia.

The glutamatergic hypothesis of schizophrenia suggests a correlation between NMDA receptor hypofunction and negative psychotic symptoms. It has been observed that the expression of the proline transporter (PROT) in the central nervous system (CNS) is associated with glutamatergic neurotransmission, as L-proline has the capacity to activate and modulate AMPA and NMDA receptors. In this study, we aimed to investigate whether inhibition of proline transporters could enhance glutamatergic neurotransmission and potentially exhibit antipsychotic effects in an experimental schizophrenia model. Using molecular dynamics analysis in silico, we validated an innovative PROT inhibitor, LQFM215. We quantified the cytotoxicity of LQFM215 in the Lund human mesencephalic cell line (LUHMES). Subsequently, we employed the ketamine-induced psychosis model to evaluate the antipsychotic potential of the inhibitor, employing behavioral tests including open-field, three-chamber interaction, and prepulse inhibition (PPI). Our results demonstrate that LQFM215, at pharmacologically active concentrations, exhibited negligible neurotoxicity when astrocytes were co-cultured with neurons. In the ketamine-induced psychosis model, LQFM215 effectively reduced hyperlocomotion and enhanced social interaction in a three-chamber social approach task across all administered doses. Moreover, the compound successfully prevented the ketamine-induced disruption of sensorimotor gating in the PPI test at all tested doses. Overall, these findings suggest that PROT inhibition could serve as a potential therapeutic target for managing symptoms of schizophrenia model.

Regioselectivity in the Nitration of Eugenol Is Independent of Inorganic Reagents: An Experimental and Theoretical Investigation with Synthetic and Mechanistic Implications.

In this study, we reinvestigated the straightforward nitration of eugenol using traditional reagents and bismuth nitrate. NMR analysis of the obtained products revealed that the regioselectivity of eugenol nitration was independent of the inorganic nitrating reagent used, consistently resulting in the formation of 6-nitroeugenol. This contradicts previous literature reports because the elusive synthesis of 5-nitroeugenol using Bi(NO3)3·5H2O was not achievable through straightforward methods; instead, this isomer could only be prepared via the well-established three-step synthesis. Theoretical investigations using DFT calculations, considering both the dielectric constant of the medium and explicit water molecules, substantiated this regioselectivity. It was found that hydration water played a critical role in the formation of a Zundel cation, shifting the thermodynamic equilibrium toward the exclusive production of 6-nitroeugenol. These results imply that all biological studies involving eugenol derivatives synthesized via direct nitration with Bi(NO3)3·5H2O should be reviewed, as they dealt with 6-substituted eugenol derivatives rather than the previously assumed 5-substituted eugenol.

L-proline transporter inhibitor (LQFM215) promotes neuroprotection in ischemic stroke.

BACKGROUND: L-proline transporter (PROT/SLC6A7) is closely associated with glutamatergic neurotransmission, where L-proline modulates the NMDA receptor (NMDAR) function. NMDAR-mediated excitotoxicity is a primary cause of neuronal death following stroke, which is triggered by the uncontrolled release of glutamate during the ischemic process. After ischemic stroke, L-proline levels show a reduction in the plasma, but high circulating levels of this molecule indicate good functional recovery. This work aimed to produce new PROT inhibitors and explore their effects on ischemic stroke. METHODS: Initially, we built a three-dimensional model of the PROT protein and run a molecular docking with the newly designed compounds (LQFM215, LQFM216, and LQFM217). Then, we synthesized new PROT inhibitors by molecular hybridization, and proline uptake was measured in ex vivo and in vivo models. The behavioral characterization of the treated mice was performed by the open-field test, elevated plus-maze, Y-maze, and forced swimming test. We used the permanent middle cerebral artery occlusion (MCAO) model to study the ischemic stroke damage and analyzed the motor impairment with limb clasping or cylinder tests. RESULTS: LQFM215 inhibited proline uptake in hippocampal synaptosomes, and the LQFM215 treatment reduced proline levels in the mouse hippocampus. LQFM215 reduced the locomotor and exploratory activity in mice and did not show any anxiety-related or working memory impairments. In the MCAO model, LQFM215 pre-treatment and treatment reduced the infarcted area and reduced motor impairments in the cylinder test and limb clasping. CONCLUSIONS: This dataset suggests that the new compounds inhibit cerebral L-proline uptake and that LQFM215 promotes neuroprotection and neuro-repair in the acute ischemic stroke model.

A t-test ranking-based discriminant analysis for classification of free-range and barn-raised broiler chickens by 1H NMR spectroscopy.

Intensive systems of raising chickens in barns prevail worldwide for financial reasons. In contrast, free-range chickens are raised in better welfare conditions, and preferred by consumers due to their distinctive taste/flavor, having higher market prices. Thus, free-range chickens have been the target of frauds. In this study, 1H NMR metabolic profiles of breasts of free-range and barn-raised broilers (108 individuals) were compared by two discriminant models, based on t-test ranking and partial least squares (PLS-DA). Both models provided 100 % of correct classification in both training and test sets, being the univariate model based on t-test screening simpler and more robust. Among other differences, barn-raised broilers presented lower carnosine and anserine concentrations, and higher free amino acids contents. Univariate discrimination was based on the ratio of two NMR signals assigned to ß-alanine and carnosine + anserine, respectively. As an additional advantage, this profiling method could be adapted to other measurement platforms.

Introducing comprehensive multiphase NMR for the analysis of food: Understanding the hydrothermal treatment of starch-based foods.

Cooking is essential for preparing starch-based food, however thermal treatment promotes the complexation of biopolymers, impacting their final properties. Comprehensive Multiphase (CMP) NMR allows all phases (liquids, gels, and solids) to be differentiated and monitored within intact samples. This study acts as a proof-of-principle to introduce CMP-NMR to food research and demonstrate its application to monitor the various phases in spaghetti, black turtle beans, and white long-grain rice, and how they change during the cooking process. When uncooked, only a small fraction of lipids and structurally bound water show any molecular mobility. Once cooked, little "crystalline solid" material is left, and all components exhibit increased molecular dynamics. Upon cooking, the solid-like components in spaghetti contains signals consistent with cellulose that were buried beneath the starches in the uncooked product. Thus, CMP-NMR holds potential for the study of food and related processes involving phase changes such as growth, manufacturing, and composting.

1H NMR as a simple methodology for differentiating barn and free-range chicken eggs.

The conventional intensive system produces cheap and safe chicken eggs, but exposes the animals to stress due to overcrowding on farms. This work compared the 1HNMR lipidic profile of chicken eggs produced in conventional and free-range systems. Sample preparation consisted of a single-step extraction and centrifugation, and the 1H NMR experimental time was just 3 min per sample. Eggs from free-range chickens had higher concentrations of ω-3 and ω-6 polyunsaturated fatty acids. The ratio between the signals at δ2.85 and 4.14 from bis-allylic polyunsaturated fatty acids and glycerol moiety, respectively, was able to correctly classify 93.8 % of the samples. These results were similar to those of PLS-DA, used for comparative purposes. Therefore, the proposed method could be easily used to assist quality control and fraud prevention in the egg industry. Free-range eggs had higher concentrations of cholesterol but, as they are smaller, similar amounts to conventional ones.

Structure-activity relationship of three new piperazine derivates with anxiolytic-like and antidepressant-like effects.

Anxiety and depression are common mental disorders affecting millions of people worldwide. Unsatisfactory clinical outcomes with the use of the available pharmacological interventions among some patients demand newer drugs with proven efficacy, safety, and tolerability profile. In this study, the LQFM211, LQFM213, and LQFM214 were designed from the piperazine scaffold and administered orally in mice. These mice were later evaluated in the open field, elevated plus maze, and forced swimming tests to assess the exploratory, anxiolytic, and antidepressant-like activities, respectively. The mechanism of action of these new derivatives was evaluated using flumazenil (benzodiazepine antagonist) and WAY100635 (5-HT1A receptor antagonist). Unlike LQFM214, the LQFM211 and LQFM213 elicited anxiolytic and antidepressant-like effects. The blockade of the effect of LQFM213 by WAY100635 suggests the involvement of the serotonergic pathway.

NMR-based metabolomics of dried berries in comparison with dietary supplements.

Consumption of dried berries is increasing worldwide due to their health benefits. This popularity has introduced berry-based supplements as an easier way to take in berry nutrients. The chemical composition of six dried berries (blueberry, cranberry, goji berry, golden berry, maqui berry, and raspberry) were compared to their berry-based supplements by metabolomics using nuclear magnetic resonance spectroscopy (NMR). Thirty-three metabolites were identified and 23 were quantified. Chemometric analysis of berries revealed that goji berry showed the highest content of amino and organic acids, while cranberry and golden berry showed a high carbohydrate content. Fatty acids were predominant in blueberry, golden berry, maqui berry, and raspberry. Additionally, an exploratory analysis of phenolic compounds in berry extracts were conducted. phenolic compounds in berry extracts could be correlated with their antioxidant activity. Additionally, derived supplements did not show similarities with their respective berry, suggesting the minimal addition of dried berry in their formulation. Thus, non-declared additives have highlighted the importance of food safety investigation.

Cashew Gum Polysaccharide Nanoparticles Grafted with Polypropylene Glycol as Carriers for Diclofenac Sodium.

This investigation focuses on the development and optimization of cashew gum polysaccharide (CGP) nanoparticles grafted with polypropylene glycol (PPG) as carriers for diclofenac sodium. The optimization of parameters affecting nanoparticles formulation was performed using a central composite rotatable design (CCRD). It was demonstrated that the best formulation was achieved when 10 mg of CGP was mixed with 10 µL of PPG and homogenized at 22,000 rpm for 15 min. The physicochemical characterization evidenced that diclofenac was efficiently entrapped, as increases in the thermal stability of the drug were observed. The CGP-PPG@diclofenac nanoparticles showed a globular shape, with smooth surfaces, a hydrodynamic diameter around 275 nm, a polydispersity index (PDI) of 0.342, and a zeta potential of -5.98 mV. The kinetic studies evidenced that diclofenac release followed an anomalous transport mechanism, with a sustained release up to 68 h. These results indicated that CGP-PPG nanoparticles are an effective material for the loading/release of drugs with similar structures to diclofenac sodium.

Neuropharmacological assessment in mice and molecular docking of piperazine derivative LQFM212.

Piperazine derivatives are an attractive class of chemical compounds for the treatment of various mental illness. Herein, we demonstrated the synthesis of LQFM212, a piperazine derivative, behavioral evaluation in mice and computational studies. In neuropharmacological assessment, LQFM212 treatment at doses of 18, 54 or 162 µmol/kg increased the sleep duration in sodium pentobarbital-induced sleep test. LQFM212 at dose of 162 µmol/kg increased climbing time in the chimney test and decreased the number of squares crossed in the open field test, suggesting that LQFM212 in high doses reduces spontaneous movement. However, LQFM212 treatment at the doses of 18 or 54 µmol/kg increased the preference for the center of field which could be indicative of anxiolytic-like effects. In elevated plus maze and light-dark box tests, LQFM212 treatment altered all parameters observed that demonstrate anxiolytic-like activity. These effects were reversed by flumazenil, mecamylamine, WAY-100635 and PCPA, but not with ketanserin, showing that anxiolytic-like activity involve benzodiazepine site of GABAA receptor, nicotinic and serotonergic pathways. Molecular docking of LQFM212 showed that the ligand has more interactions with GABAA receptor than with 5-HT1A receptor. Despite the involvement of benzodiazepine site on anxiolytic-like effect of LQFM212, treatment with this compound did not alter cognitive function in the step-down avoidance test. In this sense, this piperazine derivative is a good prototype for treating anxiety disorders with putative mechanism of action.

Nose-to-brain drug delivery mediated by polymeric nanoparticles: influence of PEG surface coating.

Intranasal administration of mucus-penetrating nanoparticles is an emerging trend to increase drug delivery to the brain. In order to overcome rapid nasal mucociliary clearance, low epithelial permeation, and local enzymatic degradation, we investigated the influence of PEGylation on nose-to-brain delivery of polycaprolactone (PCL) nanoparticles (PCL-NPs) encapsulating bexarotene, a potential neuroprotective compound. PEGylation with 1, 3, 5, and 10% PCL-PEG did not affect particle diameter or morphology. Upon incubation with artificial nasal mucus, only 5 and 10% of PCL-PEG coating were able to ensure NP stability and homogeneity in mucus. Rapid mucus-penetrating ability was observed for 98.8% of PCL-PEG5% NPs and for 99.5% of PCL-PEG10% NPs. Conversely, the motion of non-modified PCL-NPs was markedly slower. Fluorescence microscopy showed that the presence of PEG on NP surface did not reduce their uptake by RMPI 2650 cells. Fluorescence tomography images evidenced higher translocation into the brain for PCL-PEG5% NPs. Bexarotene loaded into PCL-PEG5% NPs resulted in area under the curve in the brain (AUCbrain) 3 and 2-fold higher than that for the drug dispersion and for non-PEGylated NPs (p < 0.05), indicating that approximately 4% of the dose was directly delivered to the brain. Combined, these results indicate that PEGylation of PCL-NPs with PCL-PEG5% is able to reduce NP interactions with the mucus, leading to a more efficient drug delivery to the brain following intranasal administration. Graphical abstract.

Antileishmanial activity of the chalcone derivative LQFM064 associated with reduced fluidity in the parasite membrane as assessed by EPR spectroscopy.

A novel chalcone derivative, LQFM064, demonstrated antileishmanial activity against Leishmania (L.) amazonensis, with an IC50 value of ~10 µM for the promastigote form. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled stearic acid incorporated in the plasma membrane of L. amazonensis promastigotes revealed that after 2 h of treatment with LQFM064, the parasite showed remarkable reductions in membrane fluidity. The features of the altered EPR spectra were similar to those reported for the erythrocyte membrane, which was suggested to be due to the cross-linking of oxidized hemoglobin with the cytoskeleton spectrin. In comparison to miltefosine (MIL), LQFM064 demonstrated a much lower hemolytic potential against both erythrocytes in PBS and whole blood, less cytotoxicity in J774.A1 macrophages and equivalent ability to kill parasites internalized in J774.A1 macrophages. Measurements of the IC50 values for assays with different cell concentrations enabled the estimation of the membrane-water partition coefficient (KM/W), as well as the concentrations of LQFM064 in membrane (cm50) and aqueous phase (cw50) that reduces the cell population by 50%. From the KM/W and cm50 values it was deduced that LQFM064 has a greater affinity than MIL for the parasite membrane, but the antiproliferative activity of both substances is exerted at a similar concentration in the plasma membrane.

Small-molecule MDM2 inhibitor LQFM030-induced apoptosis in p53-null K562 chronic myeloid leukemia cells.

Our group designed and synthesized the N-phenyl-piperazine LQFM030 [1-(4-((1-(4-chlorophenyl)-1H-pyrazol-4-yl)methyl) piperazin-1-yl) ethanone], a small molecule derived from molecular simplification of the Nutlin-1, an inhibitor of the human homologue of murine double minute 2 (MDM2) protein that is expressed in several types of cancer. To better investigate the effects of LQFM030 regarding the p53 mutation status, this study investigated the antiproliferative activity of LQFM030 against the p53-null K562 leukemia cells as well as the cell death pathways involved. In addition, the effects of LQFM030 on the levels of the p53/MDM2 complex were also carried out using 3T3 cells as a p53 wild-type model. Our data suggest that LQFM030 triggered apoptosis in K562 cells via different mechanisms including cell cycle arrest, caspase activation, reduction of mitochondrial activity, decrease in MDM2 expression, and transcriptional modulation of MDMX, p73, MYC, and NF-ĸB. Additionally, it promoted effects in p53/MDM2 binding in p53 wild-type 3T3 cells. Therefore, LQFM030 has antiproliferative effects in cancer cells by a p53 mutation status-independent manner with different signaling pathways. These findings open new perspectives to the treatment of leukemic cells considering the resistance development associated with cancer treatment with conventional cytotoxic drugs.

Physicochemical, structural, and thermal properties of "batata-de-teiú" starch.

Jatropha elliptica (Pohl) Muell Arg is a sub-shrub herbaceous plant native to the Brazilian Cerrado, and popularly known as "batata-de-teiú". There is lack of scientific knowledge about the structural characterization, physicochemical and technological aspects of the carbohydrate content present in Jatropha elliptica roots. Thus, this work aim contributes with new data about the evaluation of chemical-structural, thermal and technological properties of starch extracted from "batata-de-teiú". The starch presented low levels of ash, protein and total fiber and amylose content of 32.82%. The initial gelatinization temperature of "batata-de-teiú" starch was 70.1 °C, peak temperature was 73.84 °C and final 85.52 °C, and starch had low trend to retrogradation. The results of x-ray and 13C cpmass show a A-type structure with high crystallinity degree. Finally, this results suggested that the "batata-de-teiú" starch is a macromolecular structure with high branching degree, favoring intermolecular Coulomb, Van der Waals forces and hydrophobic interactions, which directly corroborated with the low solubility observed (maximum of 6.44 g·100 g-1 at 80 °C). The extraction of "batata-de-teiú" starch can be viable, and it has technological characteristics suitable for use in the food industry or pharmaceuticals, since "batata-de-teiú" starch has good thermal stability and low trend to retrogradation.

Metabolic response of soybean plants to Sclerotinia sclerotiorum infection.

White mold is a disease caused by the fungus Sclerotinia sclerotiorum, a highly destructive necrotrophic pathogen that infects soybean crops, among others. Usually, the infection triggers the plant defense system to minimize the damages. However, the effects of the infection on soybean plant metabolism are still unclear. In this work, the metabolic profiles of soybean stems and leaves were accessed using 1H HR-MAS NMR spectroscopy to identify metabolic changes as a response to S. sclerotiorum infection. This fungus widely affects the central metabolism of soybean plants, and most of the altered metabolites are involved in carbon metabolism, as suggested by the results. Furthermore, the metabolites of central metabolism can be associated with the production of several polyphenolic metabolites. Changes in metabolic profile of leaves indicate systemic effects.

A structural perspective of plant antimicrobial peptides.

Among the numerous strategies plants have developed to fend off enemy attack, antimicrobial peptides (AMPs) stand out as one of the most prominent defensive barriers that grant direct and durable resistance against a wide range of pests and pathogens. These small proteins are characterized by a compact structure and an overall positive charge. AMPs have an ancient origin and widespread occurrence in the plant kingdom but show an unusually high degree of variation in their amino acid sequences. Interestingly, there is a strikingly conserved topology among the plant AMP families, suggesting that the defensive properties of these peptides are not determined by their primary sequences but rather by their tridimensional structure. To explore and expand this idea, we here discuss the role of AMPs for plant defense from a structural perspective. We show how specific structural properties, such as length, charge, hydrophobicity, polar angle and conformation, are essential for plant AMPs to act as a chemical shield that hinders enemy attack. Knowledge on the topology of these peptides is facilitating the isolation, classification and even structural redesign of AMPs, thus allowing scientists to develop new peptides with multiple agronomical and pharmacological potential.