Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rational design of hyperstable antibacterial peptides for food preservation.

ABSTRACT: We describe the design of peptides with properties like thermostability, pH stability, and antibacterial activity against a few bacterial food pathogens. Insights obtained from classical structure-function analysis of natural peptides and their mutants through antimicrobial and enzymatic assays are used to rationally develop a set of peptides. pH and thermostability assays were performed to demonstrate robust antimicrobial activity post-treatment with high temperatures and at wide pH ranges. We have also investigated the mode of action of these hyperstable peptides using membrane permeability assays, electron microscopy, and molecular dynamics simulations. Notably, through mutational studies, we show that these peptides elicit their antibacterial action via both membrane destabilization and inhibition of intracellular trypsin-the two functions attributable to separate peptide segments. Finally, toxicity studies and food preservation assays demonstrate the safety and efficacy of the designed peptides for food preservation. Overall, the study provides a general 'blueprint' for the development of stable antimicrobial peptides (AMPs). Insights obtained from this work may also be combined with combinatorial methods in high-throughput studies for future development of antimicrobials for various applications.

SUBMITTER: Vishweshwaraiah YL

PROVIDER: S-EPMC8410836 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Accurate de novo design of hyperstable constrained peptides.

Project description:Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes that have evolved to fit precisely into binding pockets on their targets. Such peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small-molecule drugs with the specificity of much larger protein therapeutics. The ability to design constrained peptides with precisely specified tertiary structures would enable the design of shape-complementary inhibitors of arbitrary targets. Here we describe the development of computational methods for accurate de novo design of conformationally restricted peptides, and the use of these methods to design 18-47 residue, disulfide-crosslinked peptides, a subset of which are heterochiral and/or N-C backbone-cyclized. Both genetically encodable and non-canonical peptides are exceptionally stable to thermal and chemical denaturation, and 12 experimentally determined X-ray and NMR structures are nearly identical to the computational design models. The computational design methods and stable scaffolds presented here provide the basis for development of a new generation of peptide-based drugs.

| S-EPMC5161715 | biostudies-literature

Lumican Peptides: Rational Design Targeting ALK5/TGFBRI.

Project description:Lumican, a small leucine rich proteoglycan (SLRP), is a component of extracellular matrix which also functions as a matrikine regulating multiple cell activities. In the cornea, lumican maintains corneal transparency by regulating collagen fibrillogenesis, promoting corneal epithelial wound healing, regulating gene expression and maintaining corneal homeostasis. We have recently shown that a peptide designed from the 13 C-terminal amino acids of lumican (LumC13) binds to ALK5/TGFBR1 (type1 receptor of TGFβ) to promote wound healing. Herein we evaluate the mechanism by which this synthetic C-terminal amphiphilic peptide (LumC13), binds to ALK5. These studies clearly reveal that LumC13-ALK5 form a stable complex. In order to determine the minimal amino acids required for the formation of a stable lumican/ALK5 complex derivatives of LumC13 were designed and their binding to ALK5 investigated in silico. These LumC13 derivatives were tested both in vitro and in vivo to evaluate their ability to promote corneal epithelial cell migration and corneal wound healing, respectively. These validations add to the therapeutic value of LumC13 (Lumikine) and aid its clinical relevance of promoting the healing of corneal epithelium debridement. Moreover, our data validates the efficacy of our computational approach to design active peptides based on interactions of receptor and chemokine/ligand.

| S-EPMC5299588 | biostudies-literature

Rational design of glycosaminoglycan binding cyclic peptides using cPEPmatch.

Project description:Cyclic peptides present a robust platform for drug design, offering high specificity and stability due to their conformationally constrained structures. In this study, we introduce an updated version of the Cyclic Peptide Matching program (cPEPmatch) tailored for the identification of cyclic peptides capable of mimicking protein-glycosaminoglycan (GAG) binding sites. We focused on engineering cyclic peptides to replicate the GAG-binding affinity of antithrombin III (ATIII), a protein that plays a crucial role in modulating anticoagulation through interaction with the GAG heparin. By integrating computational and experimental methods, we successfully identified a cyclic peptide binder with promising potential for future optimization. MD simulations and MM-GBSA calculations were used to assess binding efficacy, supplemented by umbrella sampling to approximate free energy landscapes. The binding specificity was further validated through NMR and ITC experiments. Our findings demonstrate that the computationally designed cyclic peptides effectively target GAGs, suggesting their potential as novel therapeutic agents. This study advances our understanding of peptide-GAG interactions and lays the groundwork for future development of cyclic peptide-based therapeutics.

| S-EPMC11318538 | biostudies-literature

Rational Design and Testing of Antibacterial Aloe Vera Hemostatic Hydrogel.

Project description:Bleeding resulting from surgical procedures or trauma, including gunshot wounds, represents a life-threatening health issue. Therefore, the development of safe, effective, and convenient hemostatic agents is critical in securing the "golden time" to save patients' lives. Plant-derived compounds and plant extracts have been regarded as promising sources of hemostatic agents in previous studies, regulating hemostatic function with low toxicity and minimal side effects within the human body. Aloe vera-based hydrogels, which are characterized by flexible strength and high functionality, have emerged as a promising platform for wound applications due to their unique biocompatibility features. This study provides a comprehensive exploration of the utilization of thickening agents and natural agents such as xanthan gum, carrageenan, Carbomer, and alginate in applying aloe vera-based hydrogels as a hemostatic. Furthermore, it also tests the use of aloe vera-based hydrogels for therapeutic delivery at wound sites through the incorporation of various antimicrobial agents to extend the utility of the hydrogels beyond hemostasis. Our novel applied research utilizes aloe vera-based hydrogel as an antimicrobial hemostatic agent, providing valuable insights for a wide range of applications and highlighting its potential to enhance hemorrhage control in various emergency scenarios.

| S-EPMC11202428 | biostudies-literature

Rational design of aggregation-resistant bioactive peptides: reengineering human calcitonin.

Project description:A high propensity to aggregate into intractable deposits is a common problem limiting the production and use of many peptides and proteins in a wide range of biotechnological and pharmaceutical applications. Many therapeutic polypeptides are frequently abandoned at an early stage in their development because of problems with stability and aggregation. It has been shown recently that parameters describing the physicochemical properties of polypeptides can be used as predictors of protein aggregation. Here we demonstrate that these and similar tools can be applied to the rational redesign of bioactive molecules with a significantly reduced aggregation propensity without loss of physiological activity. This strategy has been exemplified by designing variants of the hormone calcitonin that show a significantly reduced aggregation propensity, yet maintain, or even increase, their potency when compared to the current therapeutic forms. The results suggest that this approach could be used successfully to enhance the solubility and efficacy of a wide range of other peptide and protein therapeutics.

| S-EPMC1174920 | biostudies-literature

Recent Advances in the Rational Design and Optimization of Antibacterial Agents.

Project description:This review discusses next-generation antibacterial agents developed using rational, or targeted, drug design strategies. The focus of this review is on small-molecule compounds that have been designed to bypass developing bacterial resistance, improve the antibacterial spectrum of activity, and/or to optimize other properties, including physicochemical and pharmacokinetic properties. Agents are discussed that affect known antibacterial targets, such as the bacterial ribosome, nucleic acid binding proteins, and proteins involved in cell-wall biosynthesis; as well as some affecting novel bacterial targets which do not have currently marketed agents. The discussion of the agents focuses on the rational design strategies employed and the synthetic medicinal chemistry and structure-based design techniques utilized by the scientists involved in the discoveries, including such methods as ligand- and structure-based strategies, structure-activity relationship (SAR) expansion strategies, and novel synthetic organic chemistry methods. As such, the discussion is limited to small-molecule therapeutics that have confirmed macromolecular targets and encompasses only a fraction of all antibacterial agents recently approved or in late-stage clinical trials. The antibacterial agents selected have been recently approved for use on the U.S. or European markets or have shown promising results in phase 2 or phase 3 U.S.Clinical trials

| S-EPMC5025264 | biostudies-literature

Rational design of berberine-based FtsZ inhibitors with broad-spectrum antibacterial activity.

Project description:Inhibition of the functional activity of Filamenting temperature-sensitive mutant Z (FtsZ) protein, an essential and highly conserved bacterial cytokinesis protein, is a promising approach for the development of a new class of antibacterial agents. Berberine, a benzylisoquinoline alkaloid widely used in traditional Chinese and native American medicines for its antimicrobial properties, has been recently reported to inhibit FtsZ. Using a combination of in silico structure-based design and in vitro biological assays, 9-phenoxyalkyl berberine derivatives were identified as potent FtsZ inhibitors. Compared to the parent compound berberine, the derivatives showed a significant enhancement of antibacterial activity against clinically relevant bacteria, and an improved potency against the GTPase activity and polymerization of FtsZ. The most potent compound 2 strongly inhibited the proliferation of Gram-positive bacteria, including methicillin-resistant S. aureus and vancomycin-resistant E. faecium, with MIC values between 2 and 4 µg/mL, and was active against the Gram-negative E. coli and K. pneumoniae, with MIC values of 32 and 64 µg/mL respectively. The compound perturbed the formation of cytokinetic Z-ring in E. coli. Also, the compound interfered with in vitro polymerization of S. aureus FtsZ. Taken together, the chemical modification of berberine with 9-phenoxyalkyl substituent groups greatly improved the antibacterial activity via targeting FtsZ.

| S-EPMC4019636 | biostudies-literature

Rational design of innate defense regulator peptides as tumor vaccine adjuvants.

Project description:The development of adjuvants has been an empirical process. Efforts to develop a new design and evaluation system for novel adjuvants are not only desirable but also necessary. Moreover, composite adjuvants that contain two or more types of adjuvants to synergistically enhance the immune response are important for adjuvant and vaccine design. Innate defense regulator peptides (IDRs) are promising adjuvants for clinical immunotherapy because they exhibit multifaceted immunomodulatory capabilities. However, the rational design and discovery of IDRs that have improved immunomodulatory activities have been hampered by the lack of screening techniques and the great challenges in the identification of their interaction partners. Here, we describe a screening and evaluation system for IDR design. On the basis of in vitro screening, the optimized IDR DP7 recruited neutrophils, monocytes and macrophages to the site of infection. The adjuvant, comprising the DP7 and CpG oligonucleotide (CpG), induced chemokine/cytokine expression, enhanced the antigen uptake by dendritic cells and upregulated surface marker expression in dendritic cells. Vaccination with the NY-ESO-1 or OVA antigens combined with the adjuvant alum/CpG/DP7 strongly suppressed tumor growth in mice which was due to the improvement of antigen-specific humoral and cellular immunity. Regarding the mechanism of action, GPR35 may be the potential interaction partner of DP7. Our study revealed the potential application of the screening and evaluation system as a strategy for rationally designing effective IDRs or composite adjuvants and identifying their mechanism of action.

| S-EPMC8138013 | biostudies-literature

Bioactive Peptides: Synthesis, Properties, and Applications in the Packaging and Preservation of Food.

Project description:Bioactive peptides are protein fragments which have a positive impact on the functions and conditions of living beings. Peptides have shown several useful properties for human health, including antimicrobial, antifungal, antiviral, and antitumor activities. These compounds are produced by almost all species of life. However, they are produced in limited quantities in nature. As a result, researchers have tried to synthesize bioactive peptides to study their properties and applications in various areas. Among their applications in food preservation, peptides have been incorporated into packaging materials. This review begins with a brief description of the methods used for the synthesis, purification, and characterization of peptides. Also, the main bioproperties and mechanisms of action of peptides are discussed. Finally, some applications of peptides are presented, especially their use in active packaging, their effects on the polymeric matrix, and peptide migration.

| S-EPMC7194098 | biostudies-literature

Rational design of stapled peptides targeting phosphorylated GSK3β for regulating osteoclast differentiation.

Project description:Glycogen synthase kinase-3β (GSK-3β), has been reported to show essential roles in osteoclast differentiation. Modeled after FRATtide, a peptide derived from a GSK-3 binding protein, here we designed and synthesized a series of stapled peptides targeting phosphorylated GSK3β, and evaluated the corresponding biological activities. The results indicated that stapled peptides with better helical contents and proteolytic stability than the linear ones showed improved biological activity in inhibiting osteoclast differentiation. Among them, FRC-2 and FRN-2 showed promising prospects for treating osteoporosis.

| S-EPMC9049898 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data