Peptides最新文献

{"title":"Lasso peptides realm: Insights and applications","authors":"","doi":"10.1016/j.peptides.2024.171317","DOIUrl":"10.1016/j.peptides.2024.171317","url":null,"abstract":"<div><div>Lasso peptides exhibit a range of bioactivities, including antiviral effects, inhibition of the glucagon receptor, blockade of the endothelin type B receptor, inhibition of myosin light chain kinase, and modulation of the atrial natriuretic factor, as well as notable antimicrobial properties. Intriguingly, lasso peptides exhibit remarkable proteolytic and thermal stability, addressing one of the key challenges that traditional peptides often face. The challenge in producing those valuable peptides remains the main hurdle in the way of producing larger quantities or even modifying them with more potent analogues. Genome mining and heterologous expression approaches have greatly facilitated the production of lasso peptides, moving beyond mere isolation techniques. This advancement not only allows for larger quantities but also enables the creation of additional analogues with improved stability and potency. This review aims to explore the unique bioactivities and stability of lasso peptides, along with recent advancements in genome mining and heterologous expression that address production challenges and open pathways for engineering potent analogues.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal separation alters peripheral immune responses associated with IFN-γ and OT in mice","authors":"","doi":"10.1016/j.peptides.2024.171318","DOIUrl":"10.1016/j.peptides.2024.171318","url":null,"abstract":"<div><div>The co-evolution of social behavior and the immune system plays a critical role in individuals' adaptation to their environment. However, also need for further research on the key molecules that co-regulate social behavior and immunity. This study focused on neonatal mice that were separated from their mothers for 4 hours per day between the 6th and 16th day after birth. The results showed that these mice had lower plasma levels of IFN-γ and oxytocin, but higher levels of plasma glucocorticoids (GC), then impacting their social abilities. Additionally, maternal separation led to decreased levels of <em>BDNF</em>, <em>IGF2</em>, and <em>CREB</em> mRNAs in the hippocampus, while levels in the prefrontal cortex (PFC) remained unaffected. Maternal separation also resulted in increased levels of oxytocin and <em>CRH</em> mRNA in the hypothalamus, as well as an increase in CD45⁺ lymphocyte subsets in the meninges and choroid plexus (CP), with CD8⁺ lymphocytes in meninges and CD4⁺ lymphocytes in CP showing an increase. In IFN-γ^-/- mice, a decrease in social preference was observed alongside lower plasma oxytocin levels. Moreover, IFN-γ^-/- mice exhibited reduced numbers of oxytocin neurons in the paraventricular nucleus of the paraventricular nucleus of hypothalamus (PVN), decreased <em>BDNF</em> levels in the PFC and hippocampus, and alterations in CD45⁺ lymphocytes in CP and meninges, with an increase in CD8⁺ lymphocytes in meninges and CD4⁺ lymphocytes in CP. These findings highlight the immunological impact of social stress on IFN-γ regulation, suggesting that the immunomodulatory molecule IFN-γ may influence social behavior by affecting synaptic efficiency in brain regions such as the hippocampus and PFC, which are linked to oxytocin in the PVN.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host defense peptides in crocodilians – A comprehensive review","authors":"","doi":"10.1016/j.peptides.2024.171312","DOIUrl":"10.1016/j.peptides.2024.171312","url":null,"abstract":"<div><div>Amphibians and reptiles, like all animals, are prone to periodic infections. However, crocodilians stand out for their remarkable ability to remain generally healthy and infection-free despite frequent exposure to a wide variety of microorganisms in their habitats and often sustaining significant injuries. These animals have evolved highly active immune mechanisms that provide rapid and effective defense. This is evidenced by the superior hemolytic capacity of their plasma compared to that of other organisms. To date, several host defense peptides (HDPs) have been identified in crocodilians, including cathelicidins, beta-defensins, hepcidins, leucrocins, hemocidins, and omwaprins. These peptides exhibit potent and broad-spectrum antimicrobial, antibiofilm, antifungal, and anticancer activities. Due to the relatively low but diverse evolutionary rate of crocodilians, the HDPs found in this species offer valuable insights into proteins and mechanisms of action that are highly conserved across many animals related to immune defense. The potential applications of HDPs in modern medicine represent a promising strategy for developing new therapeutic agents. Their novelty and the vast variability with which peptide sequences can be designed and modified expand the field of application for HDPs almost infinitely. This review addresses the urgent need for innovative and more effective drugs to combat the rise of antimicrobialresistant infections and evaluates the potential of crocodilian HDPs. It presents recent advances in the identification of crocodilian HDPs, particularly antimicrobial peptides (AMPs), including previously underexplored topics such as the sequential and structural conformation of different peptide types in crocodilians and the use of bioinformatics tools to enhance native peptides</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cm-p5, a molluscan-derived antifungal peptide exerts its activity by a membrane surface covering in a non-penetrating mode","authors":"","doi":"10.1016/j.peptides.2024.171313","DOIUrl":"10.1016/j.peptides.2024.171313","url":null,"abstract":"<div><div>Amidst the health crisis caused by the rise of multi-resistant pathogenic microorganisms, Antimicrobial Peptides (AMPs) have emerged as a potential alternative to traditional antibiotics. In this sense, Cm-p5 is an AMP with fungistatic activity against the yeast <em>Candida albicans</em>. Its antimicrobial activity and selectivity have been well characterized; however, the mechanism of action is still unknown. This study used biophysical approaches to gain insight into how this peptide exerts its activity. Stability and fluidity of lipid membrane were explored by liposome leakage and Laurdan generalized polarization (GP) respectively, suggesting that Cm-p5 does not perturb lipid membranes even at very high concentrations (≥100 µm.L⁻¹). Likewise, no depolarizing action was observed using 3,3′-propil-2,2′-thyodicarbocianine, a potential membrane fluorescent reporter, with <em>C. albicans</em> cells or the corresponding liposome models. Changes in liposome size were analyzed by Dynamic Light Scattering (DLS) data, indicating that Cm-p5 covers the vesicular surface slightly increasing liposome hydrodynamic size, without liposome rupture. These results were further corroborated with Langmuir monolayer isotherms, where no significant changes in lateral pressure or area per lipid were detected, indicating little or no insertion. Finally, data obtained from molecular dynamics simulations aligned with <em>in vitro</em> observations, whereby Cm-p5 slightly interacted with the fungal membrane model surface without causing significant perturbation. These results suggest Cm-p5 is not a pore-forming anti-fungal peptide and that other mechanisms of action on the membrane as some limitation of fungal nutrition or receptor-dependent transduction for depressing growth development should be explored.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of B-type natriuretic peptide gene expression in cardiomyocytes under anoxic conditions","authors":"","doi":"10.1016/j.peptides.2024.171316","DOIUrl":"10.1016/j.peptides.2024.171316","url":null,"abstract":"<div><div>Several cell biology studies have focused on the effects of hypoxic environments on cardiomyocytes. However, the effect of anoxic conditions on cardiomyocytes remains largely unexplored. In the present study, we investigated the direct effects of anoxia on B-type natriuretic peptide (BNP) gene expression in cardiomyocytes. Neonatal rat cardiomyocytes (NRCMs) were exposed to anoxia using an airtight chamber saturated with 95 % N₂/5 % CO₂. BNP mRNA levels in NRCM were substantially reduced after more than 8 h of anoxia exposure, whereas after reoxygenation, BNP gene expression levels recovered in a time-dependent manner and significantly increased after 24 h of reoxygenation. BNP mRNA levels suppressed under anoxic conditions were significantly increased by aldosterone-induced activation of sodium-proton exchanger 1 (NHE1), which was canceled by an NHE1 inhibitor, suggesting that anoxia reduces BNP gene expression, at least in part, in an NHE1-dependent manner. In summary, we found that BNP gene expression in cardiomyocytes decreases under anoxic conditions, in contrast to previous research findings that BNP expression increases under hypoxic conditions. These findings reveal a new insight that, within a single heart tissue in various cardiovascular diseases, such as myocardial infarction, the biological responses of cardiomyocytes are fundamentally different in regions of anoxia and hypoxia.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of amylin and calcitonin receptor activation by hybrid peptides","authors":"","doi":"10.1016/j.peptides.2024.171314","DOIUrl":"10.1016/j.peptides.2024.171314","url":null,"abstract":"<div><div>Calcitonin peptide hormone controls calcium homeostasis by activating the calcitonin receptor. When the calcitonin receptor forms a complex with an accessory protein, the complex functions as the receptors for another peptide hormone amylin. The amylin receptors are the drug target for diabetes and obesity treatment. Since human amylin can produce aggregates, rat amylin that does not form aggregates has been commonly used for research. Interestingly, calcitonin originated from salmons was reported to interact with human amylin receptors with higher affinity/potency than endogenous rat amylin. Here, the peptide hybrid was made of a rat amylin N-terminal fragment and a salmon calcitonin C-terminal fragment. This novel hybrid peptide showed higher potency for human amylin receptor 1/2 activation by 6- to 8-fold than endogenous rat amylin. To further examine the role of the peptide C-terminal fragment in receptor activation, another hybrid peptide was made where salmon calcitonin N-terminal 21 amino acids were fused with rat amylin C-terminal 11 amino acids. The rat amylin C-terminal fragment was previously reported to have relatively low affinity for calcitonin receptor extracellular domain. As expected, this calcitonin-amylin hybrid peptide decreased the potency for calcitonin receptor activation by 3-fold compared to salmon calcitonin. The hybrid strategy used in this study significantly changed the peptide potency for amylin and calcitonin receptor activation. These results provide insight into the role of peptide C-terminal fragments in modulating amylin and calcitonin receptor activation.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nesfatin-1 expressed in human endometrial stromal cell line (THESC) stimulates decidualization through FAK/PI3K/AKT signaling pathway","authors":"","doi":"10.1016/j.peptides.2024.171315","DOIUrl":"10.1016/j.peptides.2024.171315","url":null,"abstract":"<div><div>This study aimed to investigate the expression and functional role of nesfatin-1, a peptide hormone traditionally associated with appetite regulation, in the human endometrium. Specifically, we examined its presence and regulatory potential in the human endometrial stromal cell line, THESC cells, focusing on the process of endometrial decidualization, which is critical for implantation and pregnancy maintenance. We found that nesfatin-1 and its binding sites were expressed in THESC cells. Furthermore, nesfatin-1 protein expression decreased after treatment with 17β-estradiol but increased upon exposure to progesterone, indicating an influence of sexsteroid hormones on nesfatin-1 expression. Notably, administration of nesfatin-1 protein to THESC cells resulted in significant upregulation of genes associated with decidualization, such as insulin-like growth factor binding protein 1 (IGFBP1) and prolactin. In addition, our research showed that nesfatin-1 promotes decidualization through the activation of the FAK/PI3K/AKT signaling pathway. These findings underscore the central role of nesfatin-1 in endometrial decidualization, and suggest its potential utility in the development of new treatments to improve fertility and pregnancy outcomes.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane alteration, anti-virulence properties and metabolomic perturbation of a chionodracine-derived antimicrobial peptide, KHS-Cnd, on two bacteria models","authors":"","doi":"10.1016/j.peptides.2024.171311","DOIUrl":"10.1016/j.peptides.2024.171311","url":null,"abstract":"<div><div>Antarctic fishes, living in an extreme environment and normally exposed to pathogens, are a promising source of antimicrobial peptides (AMPs). These are emerging as next-generation drugs due to their activity against multidrug resistant (MDR) bacteria. To infect hosts, beyond intrinsic/acquired resistance, MDR species also use virulence factors such as protease secretion. Hence, AMPs targeting virulence factors could represent a novel strategy to counteract the antimicrobial resistance (AMR). In this paper, we focused on a mutant peptide, named KHS-Cnd, that was obtained from the scaffold of the chionodracine (Cnd), a natural peptide identified in the icefish <em>Chionodraco hamatus</em>. We studied different effects caused by the peptide interaction with the cell membrane of two model bacteria, <em>E. coli</em> and <em>B. cereus</em>. First, we investigated its membranolytic activity revealing that the peptide action is more evident on <em>E. coli</em>, with a 69 % uptake of the used dye at 3 μM, whereas for <em>B. cereus</em> we found only a 65 % uptake at 6 μM. Successively, we determined the impact of this lysis on total protein concentration in the medium and an increase was estimated for both bacteria (84 % after 1 h for <em>E. coli</em> and 90 % for <em>B. cereus</em>, respectively). Moreover, we evaluated the changes in the proteolytic activity of the supernatant, that is an important aspect of bacterial resistance, showing that there was a significant reduction for both bacteria, although at higher level in the case of <em>E. coli</em>. The membranolytic activity was evidenced also morphologically with TEM analysis and a different alteration was evidenced for the two bacteria. Moreover, NMR metabolomics analysis showed that peptide induces changes in <em>E. coli</em> and <em>B. cereus</em> extracellular metabolites especially at the higher tested concentrations: this metabolic variation could be used as a fingerprinting of the peptide action on bacteria physiology due to its interaction with cell wall. Finally, we determined the KHS-Cnd cytotoxicity on human primary cell lines to verify its selectivity toward bacterial cell membranes and we found low toxicity until a concentration of 5 μM. Considering that the peptide exerts both membranolytic and anti-virulence activity on <em>E. coli</em> at 1.5 μM, we confirmed the interesting potential of this AMP as a new drug to counteract AMR.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure and function of neurohypophysial hormones","authors":"","doi":"10.1016/j.peptides.2024.171300","DOIUrl":"10.1016/j.peptides.2024.171300","url":null,"abstract":"<div><div>Vasopressin (VP) and oxytocin (OXT) are neuropeptides that are synthesized in the hypothalamus and stored in/secreted from the neurohypophysis. Although VP and OXT were initially characterized as osmoregulatory and reproductive hormones, respectively, these peptides exert versatile actions not only in peripheral organs but also in the central nervous system via multiple G protein-coupled receptors. Orthologous peptides and receptors have been identified in various animal phyla, reflecting an ancient origin of this hormone family. The aim of this review is to provide basic information on this hormone family and to propose matters to be addressed in future studies. In the earlier sections of this review, we summarize the historical aspect of VP/OXT research as well as the basic features of hormonal peptides and corresponding receptors. The latter sections describe VP/OXT family peptides and their receptors in nonmammalian species, including invertebrates, to introduce the evolutionary aspect of this hormone family. By integrating knowledge from both general and comparative endocrinology perspectives, we highlight current and future research trends about the VP/OXT system.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder","authors":"","doi":"10.1016/j.peptides.2024.171301","DOIUrl":"10.1016/j.peptides.2024.171301","url":null,"abstract":"<div><div>This study investigates the rs547238576 (R150S) missense variant in the oxytocin receptor (<em>OXTR</em>) gene, previously observed through screening of rare variants in Japanese individuals with autism spectrum disorders (ASD). Contrary to the anticipated loss-of-function, R150S exhibits gain-of-function effects, enhancing oxytocin (OXT) sensitivity, ligand-binding affinity, and OXT-induced Ca²⁺ mobilization <em>in vitro</em>. This suggests R150S may alter OXT signaling, potentially contributing to the excitatory/inhibitory imbalance seen in ASD and other psychiatric disorders. Our findings underscore the significance of genetic variations in <em>OXTR</em> on functional activity and highlight the necessity for population-specific genetic study and <em>in vitro</em> analysis to elucidate genetic susceptibilities to neuropsychiatric conditions.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}