IF 2.9 4区医学

Peptides Pub Date : 2025-10-03 DOI: 10.1016/j.peptides.2025.171445

Jinfeng Pei, Guohui Wang, Minwei Yang, Liwei Liu

{"title":"Relaxin-2 Counteracts TNF-α-Induced Senescence in Human Primary Chondrocytes by Enhancing Telomerase Activity and Modulating SIRT1/p53 Signaling.","authors":"Jinfeng Pei, Guohui Wang, Minwei Yang, Liwei Liu","doi":"10.1016/j.peptides.2025.171445","DOIUrl":"https://doi.org/10.1016/j.peptides.2025.171445","url":null,"abstract":"<p><p>The pro-inflammatory cytokine TNF-α plays a crucial role in promoting cellular senescence in chondrocytes, contributing to the pathological progression of osteoarthritis (OA). Relaxin-2, a biologically active peptide hormone with diverse effects, has been investigated for its potential protective role against TNF-α-induced cellular senescence in human primary chondrocytes. In this study, human primary chondrocytes were exposed to TNF-α (10ng/mL) with and without the presence of recombinant human relaxin-2 (rh relaxin-2). SA-β-gal staining indicated that rh relaxin-2 effectively mitigated TNF-α-induced cellular senescence in these cells. Furthermore, rh relaxin-2 enhanced telomerase activity and prevented cell cycle arrest at the G0/G1 phase induced by TNF-α. Additionally, rh relaxin-2 reduced the expression levels of plasminogen activator Inhibitor-1 (PAI-1) and p21, key regulators of cellular senescence. Interestingly, TNF-α increased K382 acetylation of p53 but decreased SIRT1 expression. Notably, knocking down SIRT1 negated the protective effects of rh relaxin-2 on cellular senescence, suggesting that SIRT1 is involved in mediating the protective effects of rh relaxin-2. These findings provide new insights into the potential therapeutic use of rh relaxin-2 for OA treatment through a novel mechanism.</p>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":" ","pages":"171445"},"PeriodicalIF":2.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233179","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}

引用次数: 0

Salusin-α preserves glomerular endothelial barrier function in hypertension via YAP/ZO-1 signaling pathway Salusin-α通过YAP/ZO-1信号通路保护高血压患者肾小球内皮屏障功能

IF 2.9 4区医学

Peptides Pub Date : 2025-09-17 DOI: 10.1016/j.peptides.2025.171441

Lang Li , Huan Wang , ChunYu Zhao

{"title":"Salusin-α preserves glomerular endothelial barrier function in hypertension via YAP/ZO-1 signaling pathway","authors":"Lang Li , Huan Wang , ChunYu Zhao","doi":"10.1016/j.peptides.2025.171441","DOIUrl":"10.1016/j.peptides.2025.171441","url":null,"abstract":"<div><div>Hypertensive nephropathy (HN) is a leading cause of end-stage renal disease, driven by glomerular endothelial barrier dysfunction, inflammation, and tight junction impairment. Salusin-α, an endogenous bioactive peptide with cardiovascular protective properties, has emerged as a potential regulator of renal homeostasis, but its role in hypertensive renal injury remains unclear. This study investigated the protective effects of Salusin-α on glomerular endothelial barrier function and its underlying mechanism via the YAP/ZO-1 signaling pathway. Male C57BL/6 mice were randomized into control, angiotensin II/high-salt (ANG/HS)-induced hypertensive, and ANG/HS + Salusin-α (1 or 2 μg/kg) groups. Hypertensive mice exhibited reduced serum and renal Salusin-α levels (∼43 % and ∼55 %, respectively), increased renal inflammation (IL-1β, TNF-α, MCP-1 upregulated 2.6–3.1-fold), albuminuria (82.6 vs. 19.3 μg/day in controls), and ZO-1 downregulation (∼51 %). Salusin-α treatment dose-dependently restored ZO-1 expression (95 % of control levels at 2 μg/kg) and reduced albuminuria (∼48 %). In human renal glomerular endothelial cells (HRGECs), Salusin-α (10 nM) mitigated ANG/HS-induced barrier dysfunction (FITC-dextran flux reduced from 41.3 % to 19.6 %; TEER restored from 105.2 to 169.8 Ω·cm²) by inhibiting YAP nuclear translocation (∼52 % reduction) and preserving ZO-1. Critically, YAP overexpression abolished Salusin-α’s protective effects on ZO-1 and barrier integrity. These findings demonstrate that Salusin-α alleviates hypertensive renal injury by suppressing YAP-mediated ZO-1 degradation, thereby preserving glomerular endothelial barrier function and reducing inflammation. The study identifies Salusin-α as a novel therapeutic candidate targeting the YAP/ZO-1 axis in hypertensive nephropathy.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"193 ","pages":"Article 171441"},"PeriodicalIF":2.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092259","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}

引用次数: 0

Potential role of integrin αV as irisin receptor and advances in research 整合素αV作为鸢尾素受体的潜在作用及研究进展。

IF 2.9 4区医学

Peptides Pub Date : 2025-09-13 DOI: 10.1016/j.peptides.2025.171439

Zina Bai , Zelin Chen , Tongxinwei Sun , Cuiqing Ma , Aihong Meng

引用次数: 0

Bioactive peptides in cosmetic formulations: Review of current in vitro and ex vivo evidence 化妆品配方中的生物活性肽：目前体外和离体证据的回顾。

IF 2.9 4区医学

Peptides Pub Date : 2025-09-12 DOI: 10.1016/j.peptides.2025.171440

Nathalie van Walraven , Richard J. FitzGerald , Hans-Jürgen Danneel , Miryam Amigo-Benavent

{"title":"Bioactive peptides in cosmetic formulations: Review of current in vitro and ex vivo evidence","authors":"Nathalie van Walraven , Richard J. FitzGerald , Hans-Jürgen Danneel , Miryam Amigo-Benavent","doi":"10.1016/j.peptides.2025.171440","DOIUrl":"10.1016/j.peptides.2025.171440","url":null,"abstract":"<div><div>Bioactive peptides are increasingly employed in cosmetic products and these are generically known as cosmetic peptides. This review aims to provide an update on current information related to commercially available cosmetic peptides, and the <em>in vitro</em> and <em>ex vivo</em> evidence for their potential biological effects. A total of 102 commercially available cosmetic peptides were identified. The majority of these peptides are inspired by molecules already found in the human body, including sequences from extracellular matrix molecules, also known as matrikines. Cosmetic peptides are produced either through chemical synthesis or via biotechnological processes. Their claimed biological activities include signaling to increase collagen and hyaluronic acid production, modulation of pigmentation, maintenance of a healthy skin microbiome, antioxidant activity and cellular defense, immunomodulation, neurotransmitter inhibition, enzyme activity inhibition and trace mineral carriers. The primary structure and current scientific evidence for the bioactivities of these peptides are presented and discussed. The review highlights the diverse methodological approaches used and the outcomes measured in the assessment of cosmetic peptide efficacy. Overall, a large range of cosmetic peptides are commercially available whose efficacy is supported by divergent levels of <em>in vitro</em> and <em>ex vivo</em> data.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"193 ","pages":"Article 171440"},"PeriodicalIF":2.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065366","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}

引用次数: 0

FGF4 alleviates renal injury caused by ischemia-reperfusion(I/R) by inhibiting ferroptosis and pyroptosis FGF4通过抑制铁下垂和焦下垂减轻肾缺血再灌注（I/R）损伤

IF 2.9 4区医学

Peptides Pub Date : 2025-08-19 DOI: 10.1016/j.peptides.2025.171438

Tong Ding , Pengjie Zhang , Kunying Wang , Peng Du , Bin Duan

{"title":"FGF4 alleviates renal injury caused by ischemia-reperfusion(I/R) by inhibiting ferroptosis and pyroptosis","authors":"Tong Ding , Pengjie Zhang , Kunying Wang , Peng Du , Bin Duan","doi":"10.1016/j.peptides.2025.171438","DOIUrl":"10.1016/j.peptides.2025.171438","url":null,"abstract":"<div><div>Renal ischemia-reperfusion injury can lead to severe renal function impairment, manifested by a significant increase in serum creatinine, renal tubular obstruction, and even necrosis, which can lead to acute renal failure. This injury can also trigger systemic inflammatory response syndrome and even lead to multiple organ dysfunction. It poses a serious threat to the life and health of patients, so it is urgent to find potential drugs for treatment. In our current work, we evaluated the effects of FGFs on kidney injury caused by ischemia-reperfusion. We first established a model of kidney cell injury caused by ischemia-reperfusion. The biological functions of FGFs were further evaluated through a series of biochemical techniques. The experimental data showed that, FGFs can effectively improve the damage of kidney cells caused by ischemia-reperfusion. FGFs can alleviate iron death and pyroptosis of kidney cells caused by ischemia-reperfusion. Further work showed that FGF4 also alleviated inflammation and oxidative stress damage caused by ischemia-reperfusion. Mechanism research also showed that FGFs effectively alleviated ischemia-reperfusion-induced kidney injury by activating AMPK-mediated signaling pathways. Furthermore, in vivo, we also found that FGF4 can effectively alleviate the kidney ischemia-reperfusion injury. This finding not only indicates the potential therapeutic prospects of FGF4 for ischemic diseases, but also provides a new pharmacological target for the treatment of renal ischemia-reperfusion injury.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171438"},"PeriodicalIF":2.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895137","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}

引用次数: 0

Correlation Between decreased mixed venous oxygen saturation and increased B-type natriuretic peptides independent of hemodynamics in pre-heart failure/heart failure patients 心衰前期/心衰患者混合静脉氧饱和度降低与独立于血流动力学的b型利钠肽增加的相关性

IF 2.8 4区医学

Peptides Pub Date : 2025-07-22 DOI: 10.1016/j.peptides.2025.171433

Yusuke Kashiwagi , Tomohisa Nagoshi , Ryuji Funaki , Yuto Mashitani , Satoshi Ito , Kazuo Ogawa , Makoto Kawai , Michifumi Tokuda , Michihiro Yoshimura

{"title":"Correlation Between decreased mixed venous oxygen saturation and increased B-type natriuretic peptides independent of hemodynamics in pre-heart failure/heart failure patients","authors":"Yusuke Kashiwagi , Tomohisa Nagoshi , Ryuji Funaki , Yuto Mashitani , Satoshi Ito , Kazuo Ogawa , Makoto Kawai , Michifumi Tokuda , Michihiro Yoshimura","doi":"10.1016/j.peptides.2025.171433","DOIUrl":"10.1016/j.peptides.2025.171433","url":null,"abstract":"<div><div>Previous studies have shown that natriuretic peptides (NPs) respond to hypoxia. Mixed venous oxygen saturation (SvO₂) reflects the oxygen balance and may indicate pulmonary hypoxia. In this study, we investigated whether NPs are influenced by SvO₂ and whether this effect differs between A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in heart failure patients, using structural equation modeling (SEM). We examined 179 patients with pre-heart failure/heart failure who underwent Swan-Ganz catheterization, and investigated the relationship between NP levels and various clinical parameters, including SvO₂. The path model showed that pulmonary artery wedge pressure (PAWP) and administration of angiotensin receptor-neprilysin inhibitor (ARNI) were significantly positively associated with ANP (PAWP: standardized regression coefficient [St. β] =0.281, P = 0.002; ARNI administration: St. β=0.396, P < 0.001). PAWP and ischemic heart disease (IHD) were positively associated with BNP, whereas the estimated glomerular filtration rate (eGFR) and SvO₂ were negatively associated with BNP (PAWP: St. β =0.370, P < 0.001; IHD: St. β =0.241, P < 0.001; eGFR: St. β =-0.209, P = 0.003; SvO₂: St. β =-0.528, P < 0.001). ANP was not associated with arterial oxygen saturation (SaO₂) or SvO₂, whereas BNP showed a negative relationship with SvO₂ but was not associated with SaO₂. Thus, an increased BNP, but not ANP, correlates strongly with decreased SvO₂, an indicator of hypoxia before pulmonary circulation, independent of hemodynamic indices.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171433"},"PeriodicalIF":2.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708415","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}

引用次数: 0

Ghrelin/GHSR-1a promotes angiogenesis after myocardial infarction through the glycolytic process Ghrelin/GHSR-1a通过糖酵解过程促进心肌梗死后血管生成

IF 2.8 4区医学

Peptides Pub Date : 2025-07-22 DOI: 10.1016/j.peptides.2025.171434

Ming-Jie Yuan , Peng Zhong , Zhi-Xuan Shu , Li-Hua Zheng , Tao Liu , Song Dang

{"title":"Ghrelin/GHSR-1a promotes angiogenesis after myocardial infarction through the glycolytic process","authors":"Ming-Jie Yuan , Peng Zhong , Zhi-Xuan Shu , Li-Hua Zheng , Tao Liu , Song Dang","doi":"10.1016/j.peptides.2025.171434","DOIUrl":"10.1016/j.peptides.2025.171434","url":null,"abstract":"<div><h3>Background</h3><div>Therapeutic angiogenesis has demonstrated efficacy in revascularizing ischemic heart tissue and reducing the progression of cardiac remodeling following myocardial infarction. Recent studies have highlighted the significance of the glycolytic process in maintaining endothelial cell function and cardiac homeostasis. However, the specific role of glycolysis in angiogenesis post-myocardial infarction remains poorly understood. This study aims to explore whether ghrelin/GHSR-1a promotes angiogenesis after myocardial infarction through glycolysis.</div></div><div><h3>Methods and results</h3><div>Myocardial infarction was induced in mice, and our experiments showed that GHSR-1a overexpression led to a significant increase in the density of α-SMA-positive vessels in the peri-infarct zones, compared to the MI group, at day 7 post-infarction. Furthermore, elevated FGF-21 levels were observed in the border zone of the infarcted area seven days post-acute myocardial infarction. We also identified a modified GHSR-1a/FGF-21 axis in cardiac endothelial cells, where GHSR-1a knockdown reduced the expression of both FGF-21 and AMPK. In vitro, ghrelin enhanced glycolytic activity by increasing the expression of glycolytic enzymes. Moreover, ghrelin significantly stimulated endothelial tube formation and enhanced cell viability; however, these effects were attenuated following FGF-21 knockdown.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that ghrelin/GHSR-1a improves neovascularization and enhances glycolysis in cardiac endothelial cells by modulating FGF-21. These results lay the groundwork for further experimental and clinical investigations to explore pharmaceutical approaches for treating ischemic heart disease.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171434"},"PeriodicalIF":2.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702115","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}

引用次数: 0

Liraglutide suppresses ferroptosis by upregulation NRF2 in type 2 diabetic cardiomyopathy 利拉鲁肽通过上调2型糖尿病心肌病患者的NRF2抑制铁下垂

IF 2.8 4区医学

Peptides Pub Date : 2025-07-16 DOI: 10.1016/j.peptides.2025.171429

Xuepin Chen , Tianying Wang , Yan Gao , Guo an Wang , Jun Guan , Hongyan Dai

{"title":"Liraglutide suppresses ferroptosis by upregulation NRF2 in type 2 diabetic cardiomyopathy","authors":"Xuepin Chen , Tianying Wang , Yan Gao , Guo an Wang , Jun Guan , Hongyan Dai","doi":"10.1016/j.peptides.2025.171429","DOIUrl":"10.1016/j.peptides.2025.171429","url":null,"abstract":"<div><div>Recent research indicates that inhibiting myocardial ferroptosis may help alleviate diabetic cardiomyopathy (DCM). Liraglutide (LIRA), a glucagon-like peptide-1 receptor agonist, has been shown to offer cardiovascular protective effects. Nevertheless, the specific role of LIRA and its relationship with myocardial ferroptosis in type 2 DCM is still not well understood. An <em>in vivo</em> model of type 2 diabetes mellitus (T2DM) was created using spontaneous diabetes Goto-Kakizaki (GK) rats. These rats received LIRA at a dose of 200 μg/kg/day through daily subcutaneous injections for 8 weeks. <em>In vitro</em> experiments involved treating H9C2 cells with different concentrations of glucose, LIRA, siRNA-Nrf2, Fer-1, or their combinations. The results demonstrated that LIRA enhanced glucose metabolism, improved cardiac remodeling and function, reduced lipid peroxidation, and mitigated myocardial ferroptosis in diabetic rats. Additionally, LIRA was found to increase the levels of proteins associated with ferroptosis, such as Cyto-NRF2, Nu-NRF2, PTGS2, FTH-1, and GPX4 in DCM. <em>In vitro</em>, high glucose levels intensified the production of lipid reactive oxygen species (ROS) and lipid peroxidation, diminished mitochondrial mass, and lowered the levels of ferroptosis-related proteins, ultimately triggering ferroptosis. Notably, these detrimental effects were mitigated by LIRA treatment. Overall, these results indicate that LIRA may serve as a valuable therapeutic option for addressing myocardial ferroptosis by promoting NRF2 expression in type 2 DCM.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171429"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656018","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}

引用次数: 0

Protective effects of PACAP against high glucose-induced inflammation on air-liquid interface corneal epithelium barrier PACAP对高糖诱导炎症对角膜气液界面上皮屏障的保护作用

IF 2.8 4区医学

Peptides Pub Date : 2025-07-16 DOI: 10.1016/j.peptides.2025.171432

Grazia Maugeri , Agata Grazia D’Amico , Nicoletta Palmeri , Elisabetta Pricoco , Desiree Brancato , Concetta Federico , Velia D’Agata

{"title":"Protective effects of PACAP against high glucose-induced inflammation on air-liquid interface corneal epithelium barrier","authors":"Grazia Maugeri , Agata Grazia D’Amico , Nicoletta Palmeri , Elisabetta Pricoco , Desiree Brancato , Concetta Federico , Velia D’Agata","doi":"10.1016/j.peptides.2025.171432","DOIUrl":"10.1016/j.peptides.2025.171432","url":null,"abstract":"<div><div>Diabetes mellitus (DM) is a chronic metabolic disease considered the “epidemic” of the new millennium, with devastating impacts on quality of life and global prevalence. One of the most common ocular complications is diabetic keratopathy (DK), often overlooked compared to other diabetes-related diseases. This disease causes significant corneal damage and is characterized by an overactive inflammatory condition, alteration of the corneal epithelial barrier, and delayed wound healing. Current therapies do not always ensure effective restoration of corneal function. In our previous study, we found that changes in the endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) expression can concur for delayed epithelial wound healing in diabetic cornea. Moreover, the peptide showed cytoprotective effects on the corneal epithelium, promoting cell viability and wound healing under high glucose conditions, suggesting its potential effect in this diabetes-related disease. Therefore, this study aims to investigate the effect of PACAP against hyperglycemia-induced inflammation. To better resemble the natural conditions of corneal epithelium in vivo, an air-liquid interface (ALI) culture of the corneal epithelial cells was performed. The ALI corneal epithelium was cultured under high-glucose conditions to generate a model of DK. Our model reproduced well-established molecular and cellular characteristics of this pathology, including barrier thickness decrease and inflammation, with increased expression of IL-1β, TNF-α, and p-NF-kB. Our results indicated that PACAP significantly reduced the levels of proinflammatory cytokines IL-1β and TNF-α and inhibited the activation of NF-kB, an important mediator of inflammation. Moreover, PACAP improved epithelial morphology and corneal barrier thickness, suggesting its therapeutic potential in the treatment of DK.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171432"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656020","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}

引用次数: 0

Substitution of a proline residue in the frog skin host-defense peptide, figainin-2PL by D-lysine generates an analog with potent activity against antibiotic-resistant ESKAPE pathogens 用d -赖氨酸取代青蛙皮肤宿主防御肽中的脯氨酸残基，可以产生一种对耐抗生素ESKAPE病原体具有有效活性的类似物。

IF 2.8 4区医学

Peptides Pub Date : 2025-07-12 DOI: 10.1016/j.peptides.2025.171430

Laure Guilhaudis , Taylor S. Cunning , Jack J. Delaney , Nigel G. Ternan , Milena Mechkarska , Samir Attoub , J. Michael Conlon

{"title":"Substitution of a proline residue in the frog skin host-defense peptide, figainin-2PL by D-lysine generates an analog with potent activity against antibiotic-resistant ESKAPE pathogens","authors":"Laure Guilhaudis , Taylor S. Cunning , Jack J. Delaney , Nigel G. Ternan , Milena Mechkarska , Samir Attoub , J. Michael Conlon","doi":"10.1016/j.peptides.2025.171430","DOIUrl":"10.1016/j.peptides.2025.171430","url":null,"abstract":"<div><div>Figainin-2PL (FLGTVLKLGKAIAKTVVPMLTNAMQPKQ.NH<sub>2</sub>) is active against a range of antibiotic-resistant bacteria as well as human tumor-derived cells. The study aimed to determine the effects of a proline-substitution on the biological potency of the peptide. Secondary structure predictions indicate that figainin-2PL can adopt a helix-turn-helix conformation in membrane-mimetic environments. Circular dichroism spectra are consistent with these predictions. Replacement of the Pro<sup>18</sup> residue by either L-Ala, L-Lys or D-Lys increased the extent and stability of the helical domains. All substitutions increased cytotoxic activity against a range of human tumor-derived cells (between 1.5- and 3-fold) but major (between 4- and 10-fold) increases in hemolytic activity against mouse erythrocytes were also observed. While the substitutions Pro<sup>18</sup> → L-Ala and Pro<sup>18</sup> → L-Ala produced only minor and inconsistent changes in antibacterial activity, the [P18k] analog displayed a 2- to 4-fold greater (MIC and MBC in the range 1–8 µM) against the ESKAPE pathogens <em>Enterococcus faecalis</em>, <em>Enterococcus faecium, Klebsiella pneumoniae</em> and <em>Pseudomonas aeruginosa</em> compared with figainin-2PL and the peptide retained high potency against <em>Acinetobacter baumannii</em>, <em>Escherichia coli, Staphylococcus aureus</em> and <em>Clostridium difficile</em> (MIC and MBC = 2 µM). Consequently, the [P18k] peptide shows therapeutic potential for development into a broad-spectrum, topical antimicrobial agent.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171430"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637713","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}

引用次数: 0

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