Peptide Chain Length Research Articles

Synthetic Antimicrobial Peptides. V. Histidine-containing Antifungal Peptides with a “Linear” Type of Amphipathicity

A number of histidine-containing synthetic antifungal peptides with a “linear” type of amphipathicity (SAMP LTA) (F2Hx, H10F2, H10, where x = 7, 10, 13 and 16) have been synthesized and studied. Biological screening of such histidine-containing peptides for their antifungal and hemolytic activity was carried out. It has been shown that the presented histidine-containing SAMP LTAs are capable of effectively inhibiting the growth of opportunistic fungi Candida albicans and have low hemolytic activity in most cases not exceeding 10% even at their relatively high concentration of 400 μM in a medium containing erythrocytes. The antifungal activity of the studied peptides increases with increasing histidine residues in their composition, reaching the maximum value for the histidine-containing peptide F2H16 (MIC50 = 1.0 µM). It has been shown that as the chain length of peptides increases, their hemolytic toxicity also increases. In terms of therapeutic significance, the optimal peptides in the presented series of peptides were F2H10 and F2H13, which have higher selectivity than the short or longer peptides F2H7 or F2H16. The therapeutic index (TI) for these peptides was 233, 247, 79 and 60, respectively. It has been shown that histidine-containing derivatives of peptides with phenylalanine residues at the N-terminus of the peptide (F2H10) are less effective compared to similar peptides (H10F2) containing phenylalanine residues at the C-terminus. Among all the studied peptides, the most active was the H10 peptide (MIC50 = 0.7 µM), which does not contain phenylalanine residues, which in its antifungal activity is not only more effective than all other histidine-containing peptides, including the F2H16 peptide with 16 histidine residues, but also 4-5 times more effective than the antifungal peptide P113 (MIC50 = 3.4 µM), a short active fragment of natural histatin 5, well known in the literature. Due to its relatively low hemolytic and high antifungal activity, the presented histidine-containing SAMP LTAs have relatively high TI values, more than 60. Among all the studied peptides, peptides H10 and P113 have minimal, almost zero, hemolytic activity. However, due to its higher antifungal activity, the selectivity of peptide H10 (TI 1400) exceeds that of peptide P113 (TI 340) by more than 4 times. Thus, peptide H10, due to its high antifungal activity, low hemolytic toxicity and, accordingly, high therapeutic significance, can be used as a promising antifungal peptide drug.

Insight into the structure-activity relationship of thermal hysteresis activity of cod collagen peptides through peptidomics and bioinformatics approaches

To elucidate the correlation between variations in thermal hysteresis activity (THA) and the physicochemical properties and structure, antifreeze peptides (AFPs) of isolated fractions (CCP-1 and CCP-2) were characterized on based peptidomics and bioinformatics. The results revealed a positive correlation between the THA of cod collagen antifreeze peptide (CCAFP) and peptide chain length, isoelectric point, and hydrophobic amino acid content. Notably, the THA of CCP-1, which has higher alkaline amino acid content, was 2.60 °C at a concentration of 10 mg/mL, significantly higher than CCP (1.90 °C) and CCP-2 (2.27 °C). Glycine, proline, and valine were the vital amino acids to the formation of hydrogen bonds. Conversely, aspartic and glutamic acids at terminal regions of AFPs tended to introduce kinks in their structures. This distortion reduced binding sites for ice crystals, thereby decreasing their THA, providing a theory for understanding the physicochemical properties and structure of AFPs that influence their THA.

Low-temperature plasma jet treatment generates reactive oxygen species in solution that leads to peptide oxidation and protein aggregation

Abstract Low-temperature plasma (LTPs) jets are FDA-approved medical devices to remove cancerous tissue and aid in wound healing. However, reports on their reaction with proteins are conflicting, ranging from fragmentation, oxidation, aggregation, or a combination thereof. In this study we bridge the gap between plasma-treatment of short peptides to proteins at physiologically relevant concentrations. The LTP in this study is based on a helium dielectric barrier discharge (DBD) that forms a plasma-jet, which is directed at the solution without direct contact with the plasma, and results in the formation of reactive oxygen species (ROS) OH• and O2•- in solution. The longer the solution is treated, the more solution-phase ROS form. Treating peptide- and protein-containing solutions leads to extensive oxidation. The ROS led to the same oxidative modifications for peptide M with increasing chain length (9, 18, 37, 76 amino acids), which could be identified with high-resolution mass spectrometry. Oxidized species M+xO led to conformational changes such as compaction and elongation, while the unmodified peptide M remained unaltered, as found by ion mobility spectrometry and size exclusion chromatography. For proteins at high concentration, insoluble aggregates formed and could be identified by UV/Vis light scattering and atomic force microscopy. The formation of aggregates is dependent on the amino acid chain length, the peptide concentration, and the time for aggregate formation. These findings highlight the importance of both peptide chain length and concentration in determining the fate of peptides following the exposure to LTP, while also offering valuable insights for the field of plasma medicine. 

Translocation of Antimicrobial Peptides across Model Membranes: The Role of Peptide Chain Length.

Cushioned lipid bilayers are structures consisting of a lipid bilayer supported on a solid substrate with an intervening layer of soft material. They offer possibilities for studying the behavior and interactions of biological membranes more accurately under physiological conditions. In this work, we continue our studies of cushion formation induced by histatin 5 (24Hst5), focusing on the effect of the length of the peptide chain. 24Hst5 is a short, positively charged, intrinsically disordered saliva peptide, and here, both a shorter (14Hst5) and a longer (48Hst5) peptide variant were evaluated. Experimental surface active techniques were combined with coarse-grained Monte Carlo simulations to obtain information about these peptides. Results show that at 10 mM NaCl, both the shorter and the longer peptide variants behave like 24Hst5 and a cushion below the bilayer is formed. At 150 mM NaCl, however, no interaction is observed for 24Hst5. On the contrary, a cushion is formed both in the case of 14Hst5 and 48Hst5, and in the latter, an additional thick, diffuse, and highly hydrated layer of peptide and lipid molecules is formed, on top of the bilayer. Similar trends were observed from the simulations, which allowed us to hypothesize that positively charged patches of the amino acids lysine and arginine in all three peptides are essential for them to interact with and translocate over the bilayer. We therefore hypothesize that electrostatic interactions are important for the interaction between the solid-supported lipid bilayers and the peptide depending on the linear charge density through the primary sequence and the positively charged patches in the sequence. The understanding of how, why, and when the cushion is formed opens up the possibility for this system to be used in the research and development of new drugs and pharmaceuticals.

Chain-Length Dependence of Peptide-Lipid Bilayer Interaction Strength and Binding Kinetics: A Combined Theoretical and Experimental Approach.

Physical interactions between polypeptide chains and lipid membranes underlie critical cellular processes. Yet, despite fundamental importance, key mechanistic aspects of these interactions remain elusive. Bulk experiments have revealed a linear relationship between free energy and peptide chain length in a model system, but does this linearity extend to the interaction strength and to the kinetics of lipid binding? To address these questions, we utilized a combination of coarse-grained molecular dynamics (CG MD) simulations, analytical modeling, and atomic force microscopy (AFM)-based single molecule force spectroscopy. Following previous bulk experiments, we focused on interactions between short hydrophobic peptides (WLn, n = 1, ..., 5) with 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) bilayers, a simple system that probes peptide primary structure effects. Potentials of mean force extracted from CG MD recapitulated the linearity of free energy with the chain length. Simulation results were quantitatively connected to bulk biochemical experiments via a single scaling factor of order unity, corroborating the methodology. Additionally, CG MD revealed an increase in the distance to the transition state, a result that weakens the dependence of the dissociation force on the peptide chain length. AFM experiments elucidated rupture force distributions and, through modeling, intrinsic dissociation rates. Taken together, the analysis indicates a rupture force plateau in the WLn-POPC system, suggesting that the final rupture event involves the last 2 or 3 residues. In contrast, the linear dependence on chain length was preserved in the intrinsic dissociation rate. This study advances the understanding of peptide-lipid interactions and provides potentially useful insights for the design of peptides with tailored membrane-interacting properties.

Design Rules for the Sequestration of Viruses into Polypeptide Complex Coacervates.

Encapsulation is a strategy that has been used to facilitate the delivery and increase the stability of proteins and viruses. Here, we investigate the encapsulation of viruses via complex coacervation, which is a liquid-liquid phase separation resulting from the complexation of oppositely charged polymers. In particular, we utilized polypeptide-based coacervates and explored the effects of peptide chemistry, chain length, charge patterning, and hydrophobicity to better understand the effects of the coacervating polypeptides on virus incorporation. Our study utilized two nonenveloped viruses, porcine parvovirus (PPV) and human rhinovirus (HRV). PPV has a higher charge density than HRV, and they both appear to be relatively hydrophobic. These viruses were compared to characterize how the charge, hydrophobicity, and patterning of chemistry on the surface of the virus capsid affects encapsulation. Consistent with the electrostatic nature of complex coacervation, our results suggest that electrostatic effects associated with the net charge of both the virus and polypeptide dominated the potential for incorporating the virus into a coacervate, with clustering of charges also playing a significant role. Additionally, the hydrophobicity of a virus appears to determine the degree to which increasing the hydrophobicity of the coacervating peptides can enhance virus uptake. Nonintuitive trends in uptake were observed with regard to both charge patterning and polypeptide chain length, with these parameters having a significant effect on the range of coacervate compositions over which virus incorporation was observed. These results provide insights into biophysical mechanisms, where sequence effects can control the uptake of proteins or viruses into biological condensates and provide insights for use in formulation strategies.

Effect of different hydrolysis methods on composition and functional properties of fish protein hydrolysate obtained from Bigeye tuna waste

SummaryThe objective of this research is to investigate the impact of different hydrolysis (chemical, enzymatic and microbiological) methods of Bigeye tuna waste (Thunnus obesus) on yield, degree of hydrolysis (DH), chemical composition, amino acid profile, functional properties and microbial quality of FPH produced. The enzymatic technique produced the highest yield (11.04%) and the greatest DH (39.04%) while it gave the lowest average peptide chain length (2.56) (P < 0.05). Also, protein and fat (76.37% and 10.82%, respectively) were the highest in the enzymatic hydrolyzed fish (FPH‐E) followed by microbial fermentation (FPH‐M) (P < 0.05). In FPH‐E, FPH‐M and chemical fish protein hydrolysates (FPH‐C), the essential to non‐essential amino acid ratios were 2.43, 1.79 and 0.51, respectively. They also had good functional properties, although they were less than FPH‐C in terms of water binding capacity (3.47 and 4.18 g g−1), oil binding capacity (9.84 and 7.38 g g−1) and foaming capacity (25% and 30%, respectively), and their foam stability rate was high. All FPHs products had a low range of microbial counts, with the FPH‐M exhibiting the greatest total count of bacteria, lactic acid bacteria and moulds and yeasts. Therefore, the biologically extracted FPH especially FPH‐E has the best compositions and qualities, making them an alternative ingredient for fish meal in fish feed formulation.

Marine-Derived Bioactive Peptides Self-Assembled Multifunctional Materials: Antioxidant and Wound Healing.

Peptide self-assembling materials have received significant attention from researchers in recent years, emerging as a popular field in biological, environmental, medical, and other new materials studies. In this study, we utilized controllable enzymatic hydrolysis technology (animal proteases) to obtain supramolecular peptide self-assembling materials (CAPs) from the Pacific oyster (Crassostrea gigas). We conducted physicochemical analyses to explore the pro-healing mechanisms of CAPs on skin wounds in both in vitro and in vivo experiments through a topical application. The results demonstrated that CAPs exhibit a pH-responsive behavior for self-assembly and consist of peptides ranging from 550 to 2300 Da in molecular weight, with peptide chain lengths of mainly 11-16 amino acids. In vitro experiments indicated that CAPs display a procoagulant effect, free radical scavenging activity, and promote the proliferation of HaCaTs (112.74% and 127.61%). Moreover, our in vivo experiments demonstrated that CAPs possess the ability to mitigate inflammation, boost fibroblast proliferation, and promote revascularization, which accelerates the epithelialization process. Consequently, a balanced collagen I/III ratio in the repaired tissue and the promotion of hair follicle regeneration were observed. With these remarkable findings, CAPs can be regarded as a natural and secure treatment option with high efficacy for skin wound healing. The potential of CAPs to be further developed for traceless skin wound healing is an exciting area for future research and development.

An extracellular protease containing a novel C-terminal extension produced by a marine-originated haloarchaeon

Marine microorganisms have long been acknowledged as a significant reservoir of enzymes required for industrial use. In this study, a novel extracellular protease HslHlyB derived from marine-originated haloarchaeon Halostella pelagica DL-M4T was identified. HslHlyB contained polycystic kidney disease (PKD) domain and pre-peptidase C-terminal (PPC) domain at the C-terminus. Truncation and replacement of the C-terminal extension (CTE) of HslHlyB demonstrated the importance of the CTE in maintaining the protease activity secreted by haloarchaeon. HslHlyB and HslHlyBΔCTE were expressed in Escherichia coli BL21(DE3), and purified by high-affinity column refolding and gel filtration chromatography. The molecular masses of HslHlyB and HslHlyBΔCTE were 42 kDa and 20 kDa, respectively. The optimum catalytic reaction conditions were 50°C, pH 8.5, NaCl 3.5 M and 50°C, pH 7.5, NaCl 3 M, respectively. They showed good stability and hydrolysis capabilities towards a wide range of protein substrates. HslHlyBΔCTE showed higher catalytic reaction rate and better thermal stability than the wild type against azocasein and tetrapeptide substrate. The hydrolysates of soybean protein hydrolyzed by HslHlyBΔCTE had smaller average molecular masses and shorter average peptide chain lengths than those by HslHlyB. These results indicated the diversity of halolysins from marine-originated haloarchaea to harness organic nitrogen in the marine environment and provided promising candidates for application in various industries.

Templated Crystallization of Glycine Homopeptides: Experimental and Computational Developments

AbstractThe usage of glass beads as heterogeneous additives for the crystallization of glycine homopeptides is investigated, whereby glass beads are shown experimentally to increase the rate of crystallization. Induction time analysis indicates that the presence of glass beads acts enhances the kinetic factor for nucleation. These results are compared to those previously obtained by the authors for glycine and diglycine, and it is demonstrated that the increase in nucleation rate is proportional to the peptide chain length. Molecular dynamics simulations confirm that larger molecules exhibit faster nucleation in the presence of glass beads due to an increased number of interactions as observed with the longest hydrogen bond lifetime for triglycine, followed by diglycine and glycine.

Secondary Structure Formation in Hybrid Synthetic/Peptide Polymers: Insights from Molecular Dynamics Simulations

AbstractProteins and peptides exhibit an immense variety of structures, which are generally classified according to simple structural motifs (mainly α helices and β sheets). Considerable efforts have been invested in understanding the relationship between chemical structure (primary structure) of peptides and their spatial motifs (secondary structure). However, little is known about the possibility to interfere intentionally in these structural driving forces, for example, by inserting (short) artificial polymer chains in the peptide backbone. Structure formation on such hybrid synthetic/biochemical polymers is still an emerging field of research. Here, molecular dynamics simulations are used to illustrate the influence of inserted polyethylene segments on the secondary structure of several peptide homopolymers. A loss of structure of ≈50% when the peptide chain length drops to ten amino acids and a practically complete absence for even shorter peptide segments.

The Effect of Chain Length and Conformation on the Nucleation of Glycine Homopeptides during the Crystallization Process.

To explore the effect of chain length and conformation on the nucleation of peptides, the primary nucleation induction time of glycine homopeptides in pure water at different supersaturation levels under various temperatures has been determined. Nucleation data suggest that longer chains will prolong the induction time, especially for chains longer than three, where nucleation will occur over several days. In contrast, the nucleation rate increased with an increase in the supersaturation for all homopeptides. Induction time and nucleation difficulty increase at lower temperatures. However, for triglycine, the dihydrate form was produced with an unfolded peptide conformation (pPII) at low temperature. The interfacial energy and activation Gibbs energy of this dihydrate form are both lower than those at high temperature, while the induction time is longer, indicating the classical nucleation theory is not suitable to explain the nucleation phenomenon of triglycine dihydrate. Moreover, gelation and liquid-liquid separation of longer chain glycine homopeptides were observed, which was normally classified to nonclassical nucleation theory. This work provides insight into how the nucleation process evolves with increasing chain length and variable conformation, thereby offering a fundamental understanding of the critical peptide chain length for the classical nucleation theory and complex nucleation process for peptides.

Arginine-rich peptides as crystallization inhibitors for sodium urate.

Inhibiting the formation of urate crystals is the key to prevent hyperuricemia from developing into gout. Although many studies have focused on the influence of biomacromolecules in the crystallization behavior of sodium urate, the role of peptides with specific structures may contribute to unprecedented regulatory effects. Here, for the first time, we studied the effects of cationic peptides on the phase behavior, crystallization kinetics, and size/morphology of urate crystals. The addition of protamine (PRTM, a typical natural arginine-rich peptide) prolongs the nucleation induction time of sodium urate and inhibits crystal nucleation effectively. PRTM binds to the surface of amorphous sodium urate (ASU) through the hydrogen bond and electrostatic attraction between guanidine groups and urate anions, which is conducive to maintaining the state of ASU and inhibiting crystal nucleation. Moreover, PRTM preferentially binds to the MSUM plane and leads to a significant reduction in the aspect ratio of MSUM filamentous crystals. Further studies showed that there are significant differences in the inhibiting effects of arginine-rich peptides with different chain lengths on the crystallization behavior of sodium urate. Both guanidine functional groups and peptide chain length determine the crystallization inhibiting effect of peptides simultaneously. The present work highlights the potential role of arginine peptides in inhibiting the crystallization of urate and provides new insights into the inhibition mechanism in the pathological biomineralization of sodium urate, demonstrating the possibility of using cationic peptides to treat gout.

Development of truncated elastin-like peptide analogues with improved temperature-response and self-assembling properties

Functional peptides, which are composed of proteinogenic natural amino acids, are expected to be used as biomaterials with minimal environmental impact. Synthesizing a functional peptide with a shorter amino acid sequence while retaining its function is a easy and economical strategy. Furthermore, shortening functional peptides helps to elucidate the mechanism of their functional core region. Truncated elastin-like peptides (ELPs) are peptides consisting of repetitive sequences, derived from the elastic protein tropoelastin, that show the thermosensitive formation of coacervates. In this study, to obtain shortened ELP analogues, we synthesized several (Phe-Pro-Gly-Val-Gly)n (FPGVG)n analogues with one or two amino acid residues deleted from each repeat sequence, such as the peptide analogues consisting of FPGV and/or FPG sequences. Among the novel truncated ELP analogues, the 16-mer (FPGV)4 exhibited a stronger coacervation ability than the 25-mer (FPGVG)5. These results indicated that the coacervation ability of truncated ELPs was affected by the amino acid sequence and not by the peptide chain length. Based on this finding, we prepared Cd2+-binding sequence-conjugated ELP analogue, AADAAC-(FPGV)4, and found that it could capture Cd2+. These results indicated that the 16-mer (FPGV)4 only composed of proteinogenic amino acids could be a new biomaterial with low environmental impact.

The impact of the electric field of metal ions on the vibrations and internal hydrogen bond strength in alkali metal ion di- and triglycine complexes.

Using infrared predissociation spectroscopy of cryogenic ions, we revisit the vibrational spectra of alkali metal ion (Li+, Na+, K+) di- and triglycine complexes. We assign their most stable conformation, which involves metal ion coordination to all C=O groups and an internal NH⋯NH2 hydrogen bond in the peptide backbone. An analysis of the spectral shifts of the OH and C=O stretching vibrations across the different metal ions and peptide chain lengths shows that these are largely caused by the electric field of the metal ion, which varies in strength as a function of the square of the distance. The metal ion-peptide interaction also remotely modulates the strength of internal hydrogen bonding in the peptide backbone via the weakening of the amide C=O bond, resulting in a decrease in internal hydrogen bond strength from Li+ > Na+ > K+.

Branched short elastin-like peptides with temperature responsiveness obtained by EDTA-mediated multimerization.

Elastin-like peptides (ELPs) exhibit a reversible phase transition, known as coacervation, triggered by temperature changes. This property makes them useful as stimuli-responsive molecular materials for various applications. Among ELPs, short peptide chain lengths have some advantages over long peptide chain lengths because short ELPs can be easily obtained by chemical synthesis, allowing the use of various amino acids, including D-type and unnatural amino acids, at any position in the sequence. Moreover, the incorporated amino acids readily affect the temperature-responsive behavior of ELPs. However, to be utilized in various applications, it is necessary to develop short ELPs and to investigate their temperature-responsive properties. To obtain further insights into the temperature-responsive behavior of the short ELPs, we investigated branched short ELP analogs composed of (FPGVG)n chains (n = 1 or 2, abbreviated as F1 and F2, respectively). We synthesized multimers composed of four F1 chains or two to four F2 chains using ethylenediaminetetraacetic acid (EDTA) as a central component of multimerization. Our results show that the multimers obtained exhibited coacervation in aqueous solutions whereas linear F1 or F2 did not. Furthermore, the structural features of the obtained multimers were the same as those of linear (FPGVG)4 . In this study, we demonstrated that molecules capable of coacervation can be obtained by multimerization of F1 or F2. The temperature-responsive molecules obtained using short ELPs make it possible to use them as easy-to-synthesize peptide tags to confer temperature responsiveness to various molecules, which will aid the development of temperature-responsive biomaterials with a wide variety of functions.

Thermochemical characteristics of some glycylpeptides interaction with anionic micelles in a phosphate-buffered saline solution of sodium dodecyl sulfate

The dissolution enthalpies of glycylglycine (GlyGly), glycylglycylglycine (GlyGlyGly) and glycyl-L-tyrosine (GlyTyr) in phosphate-buffered saline solution and micellar solution (sodium dodecyl sulfate (SDS) + phosphate-buffered saline solution) were measured calorimetrically at pH = 7.4 and T = 298.15 K. The thermochemical characteristics of the interaction of peptides with micelles are defined as the transfer enthalpies of peptides into a micellar solution of sodium dodecyl sulfate in a phosphate-buffered saline solution. A comparison of the obtained results revealed the influence of the ionic state, chain length and hydrophobicity of peptides on the characteristics of their interaction with anionic micelles. The effect of micelle contraction upon interaction with peptide zwitterions was found. The differences in the dissolution enthalpies in the buffer and in pure water are described by the contributions of acid dissociation of peptides, which is accompanied by a change in the fractions of the zwitter-ionic and anionic forms with a change in pH.

Review on plant-derived bioactive peptides: biological activities, mechanism of action and utilizations in food development

Plant proteins are good alternative to animal sources in bioactive peptide production due to their safety, low-cost, rich resources and easy for large scale production. The bioactivities of the peptides derived from plant proteins including antihypertensive, hypocholesterolemic, immunomodulatory, antioxidant, antimicrobial, anti-diabetic, opiate and hepatoprotective effect are being increasingly recognized with regards to health promoting and disease prevention. In addition to bioactivities, the plant-derived bioactive peptides possess various functional properties including emulsifying and foaming properties, and water and oil retention capacities owning to the hydrophilic/lipophilic property, conformational flexibility and chain length of peptides. Hence, the plant-derived bioactive peptides are promising ingredients for the development of health-care and functional products. This review provides the research progress on the biological activities and functional properties of plant derived peptides. The mechanism of action and structure-activity relationships of the bioactive peptide were also described, when known. Furthermore, recent developments, major challenges and prospect in the application of the plant-derive bioactive peptides in the development of functional products are discussed and summarized. The objective of this review is to improve the understanding of plant-derive bioactive peptides, and provide some constructive inspirations for further research and industrial application in the food and medicine industry.

Enzyme‐assisted extraction of chicken skin protein hydrolysates and fat: Degree of hydrolysis affects the physicochemical and functional properties

AbstractEnzyme‐assisted extraction (EAE) of oils/fats involves the disruption of the cell wall of source material using enzymes to facilitate the release of oil. When proteases are used as the enzyme, EAE ends in the extracted oil as well as the protein hydrolysates. Herein, the EAE (using a commercial protease, Alcalase) was exploited to obtain fat and protein hydrolysates from chicken skin. Degree of hydrolysis (DH, the percentage ratio of cleaved peptide bonds), which showed a logarithmic correlation with the reaction time, was found to affect the properties of the products. As the DH increased, the peptide chain length of protein hydrolysates decreased which was confirmed by SDS‐PAGE analysis. With the increase of DH, the emulsifying activity index, foaming capacity, and oil holding capacity of the hydrolysates decreased but the solubility and emulsion stability index increased (p < 0.05). The DPPH free radical scavenging activity of the hydrolysates increased with the DH up to DH = 39.62% but decreased thereafter (p < 0.05). EAE resulted in a rise in fat yield and the fat contained a higher amount of unsaponifiables and lower free fatty acids (FFA) content, as compared to the control treatment (No enzyme, 80°C, 2 h, p < 0.05). DH affected the fat yield and the unsaponifiables content of the fat, positively (p < 0.05). However, it did not affect the fat FFA content and iodine value (p > 0.05). Results obtained here showed DH can be used as an effective measure for controlling the physicochemical and functional properties of chicken skin protein hydrolysates and fat in the EAE process.

Recent findings on the cellular and molecular mechanisms of action of novel food-derived antihypertensive peptides

Hypertension impacts negatively on the quality of life of sufferers, and complications associated with uncontrolled hypertension are life-threatening. Hence, many research efforts are exploring the antihypertensive properties of bioactive peptides derived from food proteins using in vitro ACE-inhibitory assay, experimentally-induced and spontaneous hypertensive rats, normotensive and hypertensive human models. In this study, the cellular and molecular mechanisms of blood pressure-lowering properties of novel peptides reported in recent studies (2015-July 30, 2021) were discussed. In addition to common mechanisms such as the inhibition of angiotensin I-converting enzyme (ACE) and renin activities, recently recognized mechanisms through which bioactive peptides exert their antihypertensive properties including the induction of vasodilation via upregulation of cyclo-oxygenase (COX) and prostaglandin receptor and endothelial nitric oxide synthase expression and L-type Ca2+ channel blockade were presented. Similarly, emerging mechanisms of blood pressure-lowering by bioactive peptides such as modulation of inflammation (TNF-α, and other cytokines signaling), oxidative stress (Keap-1/Nrf2/ARE/HO-1 and related signaling pathways), PPAR-γ/caspase3/MAPK signaling pathways and inhibition of lipid accumulation were discussed. The review also highlighted factors that influence the antihypertensive properties of peptides such as method of hydrolysis (type and number of enzymes, and chemical used for hydrolysis, and microbial fermentation), and amino acid sequence and chain length of peptides.