Peptide Secondary Structure Research Articles

A new multi-epitope DNA vaccine against Helicobacter Pylori infection in a BALB/c mouse model

BackgroundHelicobacter Pylori (H. Pylori) is a pathogen that may invade the human stomach. This bacterial strain is now causing widespread concern and considerable health issues worldwide. In contrast to antibiotic treatment, which may lead to drug resistance, vaccination therapy is emerging as a possible immunotherapy option for H. Pylori. DNA vaccines are a potential option to traditional vaccines among vaccine research methods. Furthermore, the multiepitope DNA vaccination may induce a broader immune response to suppress H. Pylori infection. MethodsFour target antigenic proteins (outer membrane beta-barrel, outer membrane beta, HofA, and hcp beta-lactamase-like protein) were used to identify epitopes. The best B and T cell epitopes were selected to induce humoral and cellular immune responses and were connected using the HEYGAEALERAG and GGGS linkers. The peptide's physicochemical characteristics, secondary and tertiary structures, antigenicity, and allergenicity were evaluated utilizing several bioinformatics tools. The multiepitope peptide was successfully inserted into the pcDNA3.1 expression vector. The immunological responses of both the vaccinated and control groups were evaluated by measuring cytokines and antibodies. ResultsBased on the data, the multiepitope peptide consists of 278 amino acid residues and has an average molecular weight (MW) of 28643.61 Da. The peptide residues were mainly situated within the preferred and permitted areas of the Ramachandran plot, accounting for 92.86% of the total. The VaxiJen server has calculated that the multiepitope peptide has an antigenicity score of 1.0067. BALB/c mice vaccinated with the DNA vaccine produced significantly higher levels of specific IgG antibodies (p<0.05). The vaccinated mice exhibited a TH1-type cellular immune response characterized by the generation of IFN-γ and a longer length of life compared to the control animals (p<0.05). In addition, the vaccination group exhibited a substantial increase in the expression level of IFN-γ and IL-1β genes compared to the control group (p<0.05). ConclusionsThe results demonstrated that the multiepitope DNA vaccine elicited significant humoral and cellular responses, and increased survival time in BALB/c mice, indicating that selecting potential epitopes may be a viable technique for developing multiepitope-based vaccines. This can help to introduce effective vaccines.

Stapled Peptides: An Innovative and Ultimate Future Drug Offering a Highly Powerful and Potent Therapeutic Alternative.

Peptide-based therapeutics have traditionally faced challenges, including instability in the bloodstream and limited cell membrane permeability. However, recent advancements in α-helix stapled peptide modification techniques have rekindled interest in their efficacy. Notably, these developments ensure a highly effective method for improving peptide stability and enhancing cell membrane penetration. Particularly in the realm of antimicrobial peptides (AMPs), the application of stapled peptide techniques has significantly increased peptide stability and has been successfully applied to many peptides. Furthermore, constraining the secondary structure of peptides has also been proven to enhance their biological activity. In this review, the entire process through which hydrocarbon-stapled antimicrobial peptides attain improved drug-like properties is examined. First, the essential secondary structural elements required for their activity as drugs are validated, specific residues are identified using alanine scanning, and stapling techniques are strategically incorporated at precise locations. Additionally, the mechanisms by which these structure-based stapled peptides function as AMPs are explored, providing a comprehensive and engaging discussion.

Fluorinated Peptide Hydrogels Result in Longer In Vivo Residence Time after Subcutaneous Administration.

Peptide-based hydrogels are of interest to biomedical applications. Herein, we have explored the introduction of fluorinated amino acids in hydrogelator H-FQFQFK-NH2 (P1) to design a series of fluorinated peptide hydrogels and evaluate the in vitro and in vivo properties of the most promising analogues. The impact of fluorinated groups on peptide gelation, secondary structure, and self-assembly processes was assessed. We show that fluorine can significantly improve hydrogel stiffness, compared to the nonfluorinated reference P1. For P15 (H-FQFQF(o-CF3)K-NH2), P18 (H-FQFQF(F5)K-NH2), and P19 (H-FQFQM(CF3)K-NH2), microscopy studies scrutinized fiber morphologies and alignment in the network. In vitro release studies of hydrogels loaded with an opioid cargo suggested improved hydrogel stability for P15 and P18. This improved stability was further validated in vivo, notably for P15, giving the most significant increased gel residence time, with more than 20% of hydrogel still present 9 days post-injection, as monitored by nuclear SPECT-CT imaging.

Genesis and regulation of C-terminal cyclic imides from protein damage.

C-Terminal cyclic imides are post-translational modifications (PTMs) that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide susceptibility to C-terminal cyclic imide formation or their effect on protein stability have not been explored in detail. Here, we characterize the primary and secondary structures of peptides and proteins that promote intrinsic formation of C-terminal cyclic imides in comparison to deamidation, a related form of protein damage. Extrinsic effects from solution properties and stressors on the cellular proteome additionally promote C-terminal cyclic imide formation on proteins like glutathione synthetase (GSS) that are susceptible to aggregation if the protein damage products are not removed by CRBN. This systematic investigation provides insight to the regions of the proteome that are prone to these unexpectedly frequent modifications, the effects of this form of protein damage on protein stability, and the biological role of CRBN.

Calcium ions do not influence the Aβ(25–35) triggered morphological changes of lipid membranes

We have studied the effect of calcium ions (Ca2+) at various concentrations on the structure of lipid vesicles in the presence of amyloid-beta peptide Aβ(25–35). In particular, we have investigated the influence of calcium ions on the formation of recently documented bicelle-like structures (BLSs) emerged as a result of Aβ(25–35) triggered membrane disintegration. First, we have shown by using small-angle X-ray and neutron scattering that peptide molecules rigidify the lipid bilayer of gel phase DPPC unilamellar vesicles (ULVs), while addition of the calcium ions to the system hinders this effect of Aβ(25–35). Secondly, the Aβ(25–35) demonstrates a critical peptide concentration at which the BLSs reorganize from ULVs due to heating and cooling the samples through the lipid main phase transition temperature (Tm). However, addition of calcium ions does not affect noticeably the Aβ-induced formation of BLSs and their structural parameters, though the changes in peptide's secondary structure, e.g. the increased α-helix fraction, has been registered by circular dichroism spectroscopy. Finally, according to 31P nuclear magnetic resonance (NMR) measurements, calcium ions do not affect the lipid-peptide arrangement in BLSs and their ability to align in the magnetic field of NMR spectrometer. The influences of various concentrations of calcium ions on the lipid-peptide interactions may prove biologically important because their local concentrations vary widely in in-vivo conditions. In the present work, calcium ions were investigated as a possible tool aimed at regulating the lipid-peptide interactions that demonstrated the disruptive effect of Aβ(25–35) on lipid membranes.

Direct hydrolysis of einkorn whole grain flour proteins for the generation of bioactive peptides using various proteases

In this study, it was aimed to investigate the direct release of BAPs from einkorn flour in one-step process. Thus, the protein extraction step was eliminated, thereby reducing processing cost. Commercial proteases (Alcalase, Flavourzyme, Neutrase, and Trypsin), and crude enzyme from Bacillus mojavensis sp. EBTA7 were used for hydrolyzing einkorn flour (30 %, w/v) solutions at 50–60 °C. The supernatants after centrifugation were used for bioactivity and techno-functionality tests. All hydrolysates demonstrated significant antioxidant capacities, with values ranging from 17.7 to 33.0 μmol TE/g for DPPH, 107 to 190 μmol TE/g for ABTS, and 0.09 to 3.08 mg EDTA/g for ion-chelating activities. Alcalase and Flavourzyme hydrolysis had the highest DPPH activities, while Bacillus mojavensis sp. EBTA7 enzyme yielded relatively high ABTS and ion-chelating activities. Notably, Bacillus mojavensis sp. EBTA7 crude enzyme hydrolysates demonstrated higher oil absorption capacity (2.94 g oil/g hydrolysate), robust emulsion (227 min), and foam stability (94 %) compared to commercial enzymes. FTIR spectroscopy confirmed variations in the secondary structure of peptides. All hydrolysates exhibited negative zeta potentials. The SDS-PAGE showcased MW ranged from 14 to 70 kDa, which was influenced by both the enzyme type and the degree of hydrolysis. Overall, Bacillus mojavensis sp. EBTA7 hydrolysates revealed considerable bio and techno-functional characteristics.

Position Matters: Pyridine Regioisomers Influence Secondary Structure and Micelle Morphology in Polymer-Homopolypeptide Micelles.

Polymer-homopolypeptide block copolymers are a class of bioinspired materials that combine the processability and stability of synthetic polymers with the biocompatibility and unique secondary structures of peptides, such as α-helices and β-sheets. These properties make them ideal candidates for a wide variety of applications, for example, in the pharmaceutical field, where they are frequently explored as building blocks for polymeric micelle drug delivery systems. While homopolypeptide side chains can be furnished with an array of different moieties to impart the copolymers with desirable properties, such as stimulus responsivity, pyridine derivatives represent an underutilized functional group for this purpose. Additionally, the interplay between polypeptide side chain structure, secondary conformation, and micelle morphology is not yet well understood, particularly in the case of structural regioisomers. Therefore, in this work, a series of polymer-homopolypeptide copolymers were prepared from a poly(ethylene glycol)-b-poly(glutamic acid) (PEG-b-PGA) backbone, where the pendant carboxylic acid groups were covalently conjugated to a series of pyridine regioisomers by carbodiimide coupling. These pyridine regioisomers differed only in the position of the nitrogen heteroatom, ortho, meta or para, relative to the linking group, generating a series of PEG-b-poly(pyridinylmethyl glutamate) (PEG-b-PMG) copolymers. Following self-assembly of the copolymers in aqueous solutions, dynamic light scattering (DLS) revealed differences in micelle hydrodynamic diameter (Dh) (ranging from ∼60 to 120 nm), while transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) revealed distinctive morphologies ranging from ellipsoidal, to cylindrical, and disc-like, suggesting that subtle changes in positional isomers in the polypeptide block may influence the micelle structure. Analysis of the PEG-b-PMG copolymer micelles by circular dichroism (CD) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy revealed that differences in the morphology were associated with changes in polypeptide secondary structure, which in turn was influenced by the position of the pyridine heteroatom. Overall, these findings contribute to the broader understanding of the relationship between polypeptide structure and micelle morphology and serve as useful insight for the rational design of polymer-polypeptide nanoparticles.

Novel BRICHOS-related Defensin-like Antimicrobial Peptide from the Marine Polychaeta Arenicola marina

Objective: To date, polychaetes remain a poorly studied class of invertebrate animals in terms of the features of functioning of their immune system and, in particular, the biodiversity of antimicrobial peptides (AMPs). AMPs also known as host defense peptides play a key role in host protection from various pathogens and regulation of the species composition of symbiotic microbes. A study of the biosynthesis of AMPs in polychaetes resulted in the discovery of the so-called BRICHOS domain in the structure of the precursor proteins of a number of such peptides. The conserved structure of this domain makes possible the bioinformatic search for AMP precursors in polychaete transcriptomes. In this work, we found and studied a novel BRICHOS-related AMP from the lugworm Arenicola marina, representing a previously undiscovered in polychaetes a structural family of defensin-like peptides stabilized by four disulfide bonds. Methods: The peptide, designated as AmBRI-44a and containing 44 amino acid residues, was obtained by heterologous expression in Escherichia coli. The peptide secondary structure was investigated by CD spectroscopy in water and dodecylphosphocholine (DPC) micelles. The minimum inhibitory concentrations (MICs) against a wide range of bacterial pathogens were assessed using the two-fold serial dilutions method. Cytotoxicity of AmBRI-44a was studied in vitro on human erythrocytes or adherent cell line HEK293T using the hemoglobin release assay or the MTT test, respectively. The AMBRI-44a potential target was discovered by successive daily subculturing of the AmBRI-44a resistant strain followed by whole-genome sequencing. Results and Discussion: According to CD data, AmBRI-44a is a predominantly β-structured peptide. AmBRI-44a was shown to have a specific activity against a narrow spectrum of Gram-positive bacteria and pronounced cytotoxic effects on the eukaryotic cell line HEK293T. The proposed mechanism of the antibacterial action of this peptide is associated with the inhibition of bacterial cell wall biosynthesis, as indicated by the genetic and phenotypic analysis of selected AmBRI-44a-resistant bacteria Bacillus licheniformis B-511. Conclusions: The resulting data allow us to consider the discovered peptide AmBRI-44a as a candidate compound for the development of an antibiotic agent that could potentially be effective in the treatment of infectious diseases mediated by multidrug-resistant Gram-positive bacteria.

Foldamers controlled by functional triamino acids: structural investigation of α/γ-hybrid oligopeptides

Peptide-like foldamers controlled by normal amide backbone hydrogen bonding have been extensively studied, and their folding patterns largely rely on configurational and conformational constraints induced by the steric properties of backbone substituents at appropriate positions. In contrast, opportunities to influence peptide secondary structure by functional groups forming individual hydrogen bond networks have not received much attention. Here, peptide-like foldamers consisting of alternating α,β,γ-triamino acids 3-amino-4-(aminomethyl)-2-methylpyrrolidine-3-carboxylate (AAMP) and natural amino acids glycine and alanine are reported, which were obtained by solution phase peptide synthesis. They form ordered secondary structures, which are dominated by a three-dimensional bridged triazaspiranoid-like hydrogen bond network involving the non-backbone amino groups, the backbone amide hydrogen bonds, and the relative configuration of the α,β,γ-triamino and α-amino acid building blocks. This additional stabilization leads to folding in both nonpolar organic as well as in aqueous environments. The three-dimensional arrangement of the individual foldamers is supported by X-ray crystallography, NMR spectroscopy, chiroptical methods, and molecular dynamics simulations.

α-Hydrazino Acid Insertion Governs Peptide Organization in Solution by Local Structure Ordering.

In this work, we have applied the concept of α-hydrazino acid insertion in a peptide sequence as a means of structurally organizing a potential protein-protein interactions (PPI) inhibitor. Hydrazino peptides characterized by the incorporation of an α-hydrazino acid at specific positions introduce an additional nitrogen atom into their backbone. This modification leads to a change in the electrostatic properties of the peptide and induces the restructuring of its hydrogen bonding network, resulting in conformational changes toward more stable structural motifs. Despite the successful use of synthetic hydrazino oligomers in binding to nucleic acids, the structural changes due to the incorporation of α-hydrazino acid into short natural peptides in solution are still poorly understood. Based on NMR data, we report structural models of p53-derived hydrazino peptides with elements of localized peptide structuring in the form of an α-, β-, or γ-turn as a result of hydrazino modification in the peptide backbone. The modifications could potentially lead to the preorganization of a helical secondary peptide structure in a solution that is favorable for binding to a biological receptor. Spectroscopically, we observed that the ensemble averaged rapidly interconverting conformations, including isomerization of the E-Z hydrazide bond. This further increases the adaptability by expanding the conformational space of hydrazine peptides as potential protein-protein interaction antagonists.

Isolation and differential structure characteristics of calcium-binding peptides derived from Pacific cod bones by hydroxyapatite affinity

Calcium-chelating peptides were found in Pacific cod bone, but their binding structure and properties have not been elucidated. Novel calcium-binding peptides were isolated by hydroxyapatite affinity chromatography (HAC), and their binding structure and properties were investigated by isothermal titration calorimetry (ITC), multispectral techniques, and mass spectrometry. Based on multiple purifications, the calcium binding capacity (CBC) of Pacific cod bone peptides (PBPs) was increased from 1.71 ± 0.15 μg/mg to 7.94 ± 1.56 μg/mg. Peptides with a molecular weight of 1–2 kDa are closely correlated with CBC. After binding to calcium, the secondary structure of peptides transitioned from random coil to β-sheet, resulting in a loose and porous microstructure. Hydrogen bonds, electrostatic interaction, and hydrophobic interaction contribute to the formation of peptide‑calcium complexes. The F21 contained 42 peptides, with repeated “GE” motif. Differential structure analysis provides a theoretical basis for the targeted preparation of high CBC peptides.

ESKtides: a comprehensive database and mining method for ESKAPE phage-derived antimicrobial peptides.

'Superbugs' have received increasing attention from researchers, such as ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.), which directly led to about 1 270 000 death cases in 2019. Recently, phage peptidoglycan hydrolases (PGHs)-derived antimicrobial peptides were proposed as new antibacterial agents against multidrug-resistant bacteria. However, there is still a lack of methods for mining antimicrobial peptides based on phages or phage PGHs. Here, by using a collection of 6809 genomes of ESKAPE isolates and corresponding phages in public databases, based on a unified annotation process of all the genomes, PGHs were systematically identified, from which peptides were mined. As a result, a total of 12 067 248 peptides with high antibacterial activities were respectively determined. A user-friendly tool was developed to predict the phage PGHs-derived antimicrobial peptides from customized genomes, which also allows the calculation of peptide phylogeny, physicochemical properties, and secondary structure. Finally, a user-friendly and intuitive database, ESKtides (http://www.phageonehealth.cn:9000/ESKtides), was designed for data browsing, searching and downloading, which provides a rich peptide library based on ESKAPE prophages and phages. Database URL: 10.1093/database/baae022.

Impact of different spacers on the conjugation between Anderson-Evans polyoxometalates and peptides

The Anderson-Evans polyoxometalates (POM) display a promising anticancer activity. The conjugation with the GRP-receptor antagonist peptide Demobesin (fQWAVGHL-NHEt) was exploited to impart cell targeting capabilities and improve the selectivity of such polyanions. However, the POM interacts with the grafted peptides, inducing chains folding and self-assembly of the resulting hybrids, thus decreasing their recognition ability. Within this context, a tailored spacer, including two domains, i.e., a hydrophilic one (1,13-diamino-4,7,10-trioxatridecan-succinamic acid, Ttds) and a tetra-anionic one (Glu-Glu-Glu-Glu-βAla, EEEE-βA) was previously utilized to mitigate such interaction. In this work, hybrid POMs containing only Ttds or EEEE-βA were prepared and the contribution of the two spacers was separately studied by using 2D NMR, fluorimetry and circular dichroism (CD). Transmission electron microscopy (TEM) was also used to observe the impact of the different spacers on self-assembly. Owing to the relevant effects observed for EEEE-βA, MD calculations were finally performed to elucidate its behavior when incorporated in the hybrid POM. Our results show that, despite the stronger impact of EEEE-βA spacer, only when both spacer are present together it is possible to observe a significant effect on the retention of peptide's secondary structure and recognition capability.

Nanogel delivery systems for cationic peptides: More than a ‘One Size Fits All’ solution

Self-assembled hyaluronic acid-based nanogels are versatile drug carriers due to their biodegradable nature and gentle preparation conditions, making them particularly interesting for delivery of peptide therapeutics. This study aims to elucidate the relation between peptide structure and encapsulation in a nanogel. Key peptide properties that affect encapsulation in octenyl succinic anhydride-modified hyaluronic acid nanogels were identified as we explored the effect on nanogel characteristics using 12 peptides with varying charge and hydrophobicity. The size and surface properties of the microfluidics-assembled peptide-loaded nanogels were evaluated using dynamic light scattering, laser Doppler electrophoresis, and small angle neutron scattering. Additionally, the change in peptide secondary structure upon encapsulation in nanogels, their release from the nanogels, and the in vitro antimicrobial activity were assessed. In conclusion, the more hydrophobic peptides showed stronger binding to the nanogel carrier and localized internally rather than on the surface of the nanogel, resulting in more spherical nanogels with smoother surfaces and slower release profiles. In contrast, cationic and hydrophilic peptides localized at the nanogel surface resulting in fluffier nanogel structures and quick and more complete release in biorelevant medium. These findings emphasize that the advantages of nanogel delivery systems for different applications depend on the therapeutic peptide properties.

Flavor Characteristics of Umami Peptides from Wuding Chicken Revealed by Molecular Dynamics Simulation.

Wuding chicken is famous for its delicious meat, and HLEEEIK, LDDALR, and ELY were jointly extracted from different processing stages of Wuding chicken. However, whether these peptides can be used as umami supplements is unclear. The sensory evaluation tests were used to study the taste characteristics. The secondary structure of the peptides and their interaction with T1R1/T1R3 were predicted by the circular dichroism spectrum and molecular dynamics simulation. The umami threshold was 0.03125 to 0.06250 mg/mL, all of which could increase umami, saltiness, sweetness, and mask bitterness. Compared with HLEEEIK, the frequency of umami active fragments and the improvement rate of the umami score of EEE increased by 133.35% and 40.09%, respectively. Peptides were dominated by umami taste according to sensory analysis, among which EE-3 (3.18) has the highest umami intensity followed by LR-4 (2.58), HK-7 (2.13), and EY-3 (1.82). The main secondary structure of umami peptides was β-folding, and Tyr74, Arg323, Arg272, and Gln35 were the key amino acid residues for binding of umami peptides to the receptor. This study further elucidated that the umami intensity of the peptides could be altered by changing the sequence composition of the peptides, which enhanced our understanding of the complex flavor properties of umami peptides.

Hidden imaging in thin polymer films with embedded fluorescent peptide nanodots.

Fluorescent (FL) encrypting nanostructures, such as quantum dots, carbon dots, organic dyes, lanthanide nanocrystals, DNA, and more, are effective tools for advanced applications in high-resolution hidden imaging. These applications include tracking, labeling, security printing, and anti-counterfeiting drug technology. In this work, what we believe to be a new FL encoding nanostructures has been proposed, which consists of recently discovered nanometer-scale peptide dots. When refolded into a beta-sheet peptide secondary structure, these biocompatible nanoparticles exhibit a strong and tunable FL effect. The biophotonic FL covers the entire visible spectrum, making the peptide dots next-generation nanoscale light sources with a quantum yield of 30%. Our studies demonstrate that these FL bio-nanodots also exhibit a significant irreversible photo-bleaching effect associated with the light-induced destruction of noncovalent intermolecular hydrogen bonds of the peptide dots' highly stable beta-sheet secondary structure. We present what we believe is a new approach for achieving high-resolution long-term optical memory by tailoring various hidden images in the developed thin polyvinyl alcohol (PVA) polymer films with an embedded dense array of FL peptide nanodots. The technology enables recording photo-bleached patterns, barcodes, and high-resolution images.

Structure and Function of Canine SP-C Mimic Proteins in Synthetic Surfactant Lipid Dispersions.

Lung surfactant is a mixture of lipids and proteins and is essential for air breathing in mammals. The hydrophobic surfactant proteins B and C (SP-B and SP-C) assist in reducing surface tension in the lung alveoli by organizing the surfactant lipids. SP-B deficiency is life-threatening, and a lack of SP-C can lead to progressive interstitial lung disease. B-YL (41 amino acids) is a highly surface-active, sulfur-free peptide mimic of SP-B (79 amino acids) in which the four cysteine residues are replaced by tyrosine. Mammalian SP-C (35 amino acids) contains two cysteine-linked palmitoyl groups at positions 5 and 6 in the N-terminal region that override the β-sheet propensities of the native sequence. Canine SP-C (34 amino acids) is exceptional because it has only one palmitoylated cysteine residue at position 4 and a phenylalanine at position 5. We developed canine SP-C constructs in which the palmitoylated cysteine residue at position 4 is replaced by phenylalanine (SP-Cff) or serine (SP-Csf) and a glutamic acid-lysine ion-lock was placed at sequence positions 20-24 of the hydrophobic helical domain to enhance its alpha helical propensity. AI modeling, molecular dynamics, circular dichroism spectroscopy, Fourier Transform InfraRed spectroscopy, and electron spin resonance studies showed that the secondary structure of canine SP-Cff ion-lock peptide was like that of native SP-C, suggesting that substitution of phenylalanine for cysteine has no apparent effect on the secondary structure of the peptide. Captive bubble surfactometry demonstrated higher surface activity for canine SP-Cff ion-lock peptide in combination with B-YL in surfactant lipids than with canine SP-Csf ion-lock peptide. These studies demonstrate the potential of canine SP-Cff ion-lock peptide to enhance the functionality of the SP-B peptide mimic B-YL in synthetic surfactant lipids.

Antimicrobial peptide interactions with bacterial cell membranes

Antimicrobial peptides (AMPs) are potential alternatives for common antibiotics because of their greater activity and efficiency against a broad range of viruses, bacteria, fungi, and parasites. In this project, two antimicrobial peptides including magainin 2 and protegrin 1 with α-helix and β-sheet secondary structures were selected to investigate their interactions with different lipid bilayers such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine (POPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), POPC/POPG (7:3), POPC/POPS (7:3), POPG/POPE(1:3), and POPG/POPE(3:1). The obtained structures of the AMPs illustrated that protegrin 1 cannot maintain its secondary structure in the solution phase in contrast to magainin 2. The head groups of the lipid units play a key role in the stability of the lipid bilayers. The head parts of the lipid membranes by increasing the internal H-bond contribute to membrane compactness. The POPG and POPS units inside the POPC/POPG and POPC/POPS membranes increase the order of the POPC units. The cationic residues of the AMPs form remarkable electrostatic interactions with the negatively charged membrane surfaces, which play a key role in the stabilization process of the peptide secondary structures. The Arg residues of protegrin 1 and the Gly1, Lys4, Lys10, Lys11, Lys14, and Glu19 of the magainin 2 have the most important roles in the complexation process. The values of Gibbs binding energies (ΔG) indicate that the complexation process between AMPs and different bacterial membranes is favorable from the thermodynamic viewpoint and AMPs could form stable complexes with the lipid bilayers. As a result of ΔG values, protegrin 1 forms a more stable complex with POPG/POPE(3:1), while the α-helix has more affinity to the POPG/POPE(1:3) bacterial membranes. Therefore, it can be considered that β-sheet and α-helix AMPs are more effective against gram-positive and gram-negative bacteria, respectively. The results of this study can provide useful details about the antimicrobial peptide interactions with the bacterial cell, which can be employed for designing new antimicrobial materials with greater efficiency. Communicated by Ramaswamy H. Sarma

Functional oligo- and polypeptide assemblies for photochemical, optical and electronic applications.

The primary and secondary structures of peptides are useful as scaffolds to sequentially arrange functional groups of molecules. In this review, we review self-assembled functional peptides, whereby peptides with appropriate amino acid sequences can assemble using functional groups on their side chains. First, we apply our design strategies for the synthesis of peptide-based materials with sequenced side chains with polar moieties, organic dyes and metal complexes. The synthetic oligopeptides thus obtained exhibit inherent photoinduced charge separation and electrochemical redox activities, as well as responses to bio-sequences. Next, catalytic and photocatalytic oxidation reduction reactions and hydrogen evolution reactions are shown by utilizing the peptides with separated functionalities on both sides of β-sheets by hybridizing with electro- and photoactive graphene oxide and metal nanoparticles. Finally, the self-assembled natural proteins that form micrometre-scale spherical geometry and fibres are utilized for optical and electronic applications. The silk fibroin forms well-defined microspheres with smooth surface morphology, leading to properties suitable for use in optical resonators, which can sense external humidity because of the hygroscopic nature of silk fibroin. Dragline silk fibres can act as optical waveguides that can perform intermediate natural polymer-based optical logic operations. These functional peptides are utilizable for various applications in catalysis, optics and electronics.

Capping motifs in antimicrobial peptides and their relevance for improved biological activities.

N-capping (N-cap) and C-capping (C-cap) in biologically active peptides, including specific amino acids or unconventional group motifs, have been shown to modulate activity against pharmacological targets by interfering with the peptide's secondary structure, thus generating unusual scaffolds. The insertion of capping motifs in linear peptides has been shown to prevent peptide degradation by reducing its susceptibility to proteolytic cleavage, and the replacement of some functional groups by unusual groups in N- or C-capping regions in linear peptides has led to optimized peptide variants with improved secondary structure and enhanced activity. Furthermore, some essential amino acid residues that, when placed in antimicrobial peptide (AMP) capping regions, are capable of complexing metals such as Cu2+, Ni2+, and Zn2+, give rise to the family known as metallo-AMPs, which are capable of boosting antimicrobial efficacy, as well as other activities. Therefore, this review presents and discusses the different strategies for creating N- and C-cap motifs in AMPs, aiming at fine-tuning this class of antimicrobials.