Biochimie最新文献

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Tailor-made vincristine-liposomes for tumor targeting "用于肿瘤靶向的定制长春新碱脂质体"。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.017
Ariana Abawi , Ana-Maria Trunfio-Sfarghiu , Céline Thomann , Emma Petiot , Giovanna Lollo , Thierry Granjon , Agnès Girard-Egrot , Ofelia Maniti
{"title":"Tailor-made vincristine-liposomes for tumor targeting","authors":"Ariana Abawi ,&nbsp;Ana-Maria Trunfio-Sfarghiu ,&nbsp;Céline Thomann ,&nbsp;Emma Petiot ,&nbsp;Giovanna Lollo ,&nbsp;Thierry Granjon ,&nbsp;Agnès Girard-Egrot ,&nbsp;Ofelia Maniti","doi":"10.1016/j.biochi.2024.07.017","DOIUrl":"10.1016/j.biochi.2024.07.017","url":null,"abstract":"<div><div>To ensure selective targeting based on membrane fluidity and physico-chemical compatibility between the biological membrane of the target cell and the lipid membrane of the liposomes carriers. Lipid-based carriers as liposomes with varying membrane fluidities were designed for delivering vincristine, an anti-tumor compound derived from Madagascar's periwinkle. Liposomes, loaded with vincristine, were tested on prostate, colon, and breast cancer cell lines alongside non-tumor controls. Results showed that vincristine-loaded liposomes with fluid membranes significantly decreased the viability of cancer cell lines compared to controls. Confocal microscopy revealed the intracellular release of vincristine, evidenced by disrupted mitosis-specific labeling of actin filaments in metastatic prostate cell lines. This highlights the crucial role of membrane fluidity in the development of lipid-based drug carriers, offering a promising and cost-effective option for targeting cancer cells as an alternative to conventional strategies.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 35-46"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systemic and joint adipose tissue lipids and their role in osteoarthritis 全身和关节脂肪组织脂质及其在骨关节炎中的作用。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.09.015
Natalia Zapata-Linares , Léa Loisay , Diego de Haro , Francis Berenbaum , Thomas Hügle , Jeroen Geurts , Xavier Houard
{"title":"Systemic and joint adipose tissue lipids and their role in osteoarthritis","authors":"Natalia Zapata-Linares ,&nbsp;Léa Loisay ,&nbsp;Diego de Haro ,&nbsp;Francis Berenbaum ,&nbsp;Thomas Hügle ,&nbsp;Jeroen Geurts ,&nbsp;Xavier Houard","doi":"10.1016/j.biochi.2024.09.015","DOIUrl":"10.1016/j.biochi.2024.09.015","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a major disease whose prevalence increases with aging, sedentary lifestyles, and obesity. The association between obesity and OA has been well documented, but the precise mechanisms underlying this heightened risk remain unclear. While obesity imposes greater forces on joints, systemic fat-derived factors such as lipids or adipokine may potentially act on the pathophysiology of OA, but the exact role of these factors in weight-bearing and non-weight-bearing joints remains elusive. Intra-articular adipose tissues (IAAT) have gained significant attention for actively participating in OA pathogenesis by interacting with various joint tissues. Lipid content has been proposed as a diagnostic target for early OA detection and a potential source of biomarkers. Moreover, targeting a specific IAAT called infrapatellar fat pad (IFP) and its lipids hold promise for attenuating OA-associated inflammation. Conversely, bone marrow adipose tissue (BMAT), which was long thought to be an inert filling tissue, is now increasingly considered a dynamic tissue whose volume and lipid content regulate bone remodeling in pathological conditions. Given OA's ability to alter adipose tissues, particularly those within the joint (IFP and BMAT), and the influence of adipose tissues on OA pathogenesis, this review examines the lipids produced by OA-associated adipose tissues, shedding light on their potential role in OA pathophysiology and highlighting them as potential therapeutic targets.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 130-138"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unlocking the potential of histone modification in regulating bone metabolism 挖掘组蛋白修饰在调节骨代谢中的潜力。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.08.004
Jiayuan Zhang, Hanghang Liu, Yao Liu, En Luo, Shibo Liu
{"title":"Unlocking the potential of histone modification in regulating bone metabolism","authors":"Jiayuan Zhang,&nbsp;Hanghang Liu,&nbsp;Yao Liu,&nbsp;En Luo,&nbsp;Shibo Liu","doi":"10.1016/j.biochi.2024.08.004","DOIUrl":"10.1016/j.biochi.2024.08.004","url":null,"abstract":"<div><div>Bone metabolism plays a crucial role in maintaining normal bone tissue homeostasis and function. Imbalances between bone formation and resorption can lead to osteoporosis, osteoarthritis, and other bone diseases. The dynamic and complex process of bone remodeling is driven by various factors, including epigenetics. Histone modification, one of the most important and well-studied components of epigenetic regulation, has emerged as a promising area of research in bone metabolism. Different histone proteins and modification sites exert diverse effects on osteogenesis and osteoclastogenesis. In this review, we summarize recent progress in understanding histone modifications in bone metabolism, including specific modification sites and potential regulatory enzymes. Comprehensive knowledge of histone modifications in bone metabolism could reveal new therapeutic targets and treatment strategies for bone diseases.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 286-298"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibitors and activators for myotoxic phospholipase A2-like toxins from snake venoms – A structural overview 蛇毒中肌毒性磷脂酶 A2 类毒素的抑制剂和激活剂--结构概述。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.016
Guilherme H.M. Salvador , Fábio F. Cardoso , Bruno Lomonte , Marcos R.M. Fontes
{"title":"Inhibitors and activators for myotoxic phospholipase A2-like toxins from snake venoms – A structural overview","authors":"Guilherme H.M. Salvador ,&nbsp;Fábio F. Cardoso ,&nbsp;Bruno Lomonte ,&nbsp;Marcos R.M. Fontes","doi":"10.1016/j.biochi.2024.07.016","DOIUrl":"10.1016/j.biochi.2024.07.016","url":null,"abstract":"<div><div>Snakebite envenomations result in acute and chronic physical and psychological health effects on their victims, leading to a substantial socio-economic burden in tropical and subtropical countries. Local necrosis is one of the serious effects caused by envenomation, primarily induced by snake venoms from the Viperidae family through the direct action of components collectively denominated as myotoxins, including the phopholipase A<sub>2</sub>-like (PLA<sub>2</sub>-like) toxins. Considering the limitations of antivenoms in preventing the rapid development of local tissue damage caused by envenomation, the use of small molecule therapeutics has been suggested as potential first-aid treatments or as adjuvants to antivenom therapy. In this review, we provide an overview of the structural interactions of molecules exhibiting inhibitory activity toward PLA<sub>2</sub>-like toxins. Additionally, we discuss the implications for the myotoxic mechanism of PLA<sub>2</sub>-like toxins and the molecules involved in their activation, highlighting key differences between activators and inhibitors. Finally, we integrate all these results to propose a classification of inhibitors into three different classes and five sub-classes. Taking into account the structural and affinity information, we compare the different inhibitors/ligands to gain a deeper understanding of the structural basis for the effective inhibition of PLA<sub>2</sub>-like toxins. By offering these insights, we aim to contribute to the search for new and efficient inhibitor molecules to complement and improve current therapy by conventional antivenoms.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 231-247"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lipids, from molecular mechanisms to diseases 脂质,从分子机制到疾病。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.11.001
Isabelle Dugail , Sylvie Demignot , Lhousseine Touqui , Abdou Rachid Thiam
{"title":"Lipids, from molecular mechanisms to diseases","authors":"Isabelle Dugail ,&nbsp;Sylvie Demignot ,&nbsp;Lhousseine Touqui ,&nbsp;Abdou Rachid Thiam","doi":"10.1016/j.biochi.2024.11.001","DOIUrl":"10.1016/j.biochi.2024.11.001","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 1-2"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glucose concentration is determinant for the functioning of hydrogenase 1 and hydrogenase 2 in regulating the proton and potassium fluxes in Escherichia coli at pH 7.5 在 pH 值为 7.5 的大肠杆菌中,葡萄糖浓度对氢化酶 1 和氢化酶 2 调节质子和钾通量的功能起着决定性作用。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.013
Liana Vanyan , Karen Trchounian
{"title":"Glucose concentration is determinant for the functioning of hydrogenase 1 and hydrogenase 2 in regulating the proton and potassium fluxes in Escherichia coli at pH 7.5","authors":"Liana Vanyan ,&nbsp;Karen Trchounian","doi":"10.1016/j.biochi.2024.07.013","DOIUrl":"10.1016/j.biochi.2024.07.013","url":null,"abstract":"<div><div>This study examines how F<sub>O</sub>F<sub>1</sub>-ATPase, hydrogenases (Hyd-1 and Hyd-2), and potassium transport systems (TrkA) interact to maintain the proton motive force (<em>pmf</em>) in <em>E. coli</em> during fermentation of different glucose concentrations (2 g L<sup>−1</sup> and 8 g L<sup>−1</sup>). Our findings indicate that mutants lacking the <em>hyaA-hyaC</em> genes exhibited a 30 % increase in total proton flux compared to the wild type when grown with 2 g L<sup>−1</sup> glucose. This has been observed during assays where similar glucose levels were supplemented. Disruptions in proton pumping, particularly in <em>hyaB</em> and <em>hyaC</em> single mutants, led to increased potassium uptake. The <em>hyaB</em> mutant showed a threefold increase in the contribution of F<sub>O</sub>F<sub>1</sub>-ATPase to proton flux, suggesting a significant role for Hyd-1 in proton translocation. In the <em>hybC</em> mutant grown in 2 g L<sup>−1</sup> glucose conditions, DCCD-sensitive fluxes decreased by 70 %, indicating critical role of Hyd-2 in proton transport and F<sub>O</sub>F<sub>1</sub> function. When cells were grown with 8 g L<sup>−1</sup> glucose, the 2H<sup>+</sup>/1K<sup>+</sup> ratio was significantly disturbed in both wild type and mutants. Despite these perturbances, mutants with disruptions in Hyd-1 and Hyd-2 maintained constant F<sub>O</sub>F<sub>1</sub> function, suggesting that this enzyme remains stable in glucose-rich environments. These results provide valuable insights into how Hyd-1 and Hyd-2 contribute to the regulation of ion transport, particularly proton translocation, in response to glucose concentration. Our study uncovered potential complementary mechanisms between Hyd-1 and Hyd-2 subunits, suggesting a complex interplay between these enzymes via metabolic cross talk with F<sub>O</sub>F<sub>1</sub> in response to glucose concentrations to maintain <em>pmf</em>.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 205-216"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alpha hemolysin of Escherichia coli induces a necrotic-like procoagulant state in platelets 大肠杆菌的α溶血素诱导血小板出现类似坏死的促凝血状态。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.06.001
Kenia Pérez Vázquez , Julia Tau , M. Florencia Leal Denis , Claudio M. Fader , Mariano A. Ostuni , Pablo J. Schwarzbaum , Vanesa Herlax
{"title":"Alpha hemolysin of Escherichia coli induces a necrotic-like procoagulant state in platelets","authors":"Kenia Pérez Vázquez ,&nbsp;Julia Tau ,&nbsp;M. Florencia Leal Denis ,&nbsp;Claudio M. Fader ,&nbsp;Mariano A. Ostuni ,&nbsp;Pablo J. Schwarzbaum ,&nbsp;Vanesa Herlax","doi":"10.1016/j.biochi.2024.06.001","DOIUrl":"10.1016/j.biochi.2024.06.001","url":null,"abstract":"<div><div>Uropathogenic strains of <em>E. coli</em><span><span> (UPEC) is a leading cause of sepsis, deploying multiple </span>virulence factors<span><span><span> to evade host immune responses. Notably, alpha-hemolysin (HlyA) produced by UPEC is implicated in septic symptoms associated with </span>bacteremia, correlating with </span>thrombocytopenia, a critical indicator of organ dysfunction and a predictor of poorer patient prognosis.</span></span></div><div><span><span>This study meticulously explores the impact of sublytic concentrations of HlyA on platelets. Findings reveal that HlyA triggers an increase in intracellular calcium, activating </span>calpain<span> and exposing phosphatidylserine to the cell surface, as validated by flow cytometric experiments. </span></span>Electron microscopy<span><span> reveals a distinctive balloon-like shape in HlyA-treated platelets, indicative of a procoagulant state. The toxin induces the release of procoagulant extracellular vesicles and the secretion of alpha and </span>dense granules. Overall, the results point to HlyA inducing a necrotic-like procoagulant state in platelets.</span></div><div>The effects of sublytic concentrations of HlyA on both erythrocytes and platelets could have a potential impact on capillary microcirculation<span>. Targeting HlyA emerges as a viable therapeutic strategy to mitigate the adverse effects of UPEC infections, especially in South American countries where these infections are endemic, underscoring its significance as a potential therapeutic target.</span></div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 1-14"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stealing survival: Iron acquisition strategies of Mycobacterium tuberculosis 偷窃生存:结核分枝杆菌的铁获取策略。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.06.006
Gauri Shankar, Yusuf Akhter
{"title":"Stealing survival: Iron acquisition strategies of Mycobacterium tuberculosis","authors":"Gauri Shankar,&nbsp;Yusuf Akhter","doi":"10.1016/j.biochi.2024.06.006","DOIUrl":"10.1016/j.biochi.2024.06.006","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (<em>Mtb</em>), the causative agent of tuberculosis (TB), faces iron scarcity within the host due to immune defenses. This review explores the importance of iron for <em>Mtb</em> and its strategies to overcome iron restriction. We discuss how the host limits iron as an innate immune response and how <em>Mtb</em> utilizes various iron acquisition systems, particularly the siderophore-mediated pathway. The review illustrates the structure and biosynthesis of mycobactin, a key siderophore in <em>Mtb</em>, and the regulation of its production. We explore the potential of targeting siderophore biosynthesis and uptake as a novel therapeutic approach for TB. Finally, we summarize current knowledge on <em>Mtb</em>'s iron acquisition and highlight promising directions for future research to exploit this pathway for developing new TB interventions.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 37-60"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A review on the diversity of antimicrobial peptides and genome mining strategies for their prediction 抗菌肽多样性及其预测基因组挖掘策略综述。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.06.013
Naveen Kumar, Prashant Bhagwat, Suren Singh, Santhosh Pillai
{"title":"A review on the diversity of antimicrobial peptides and genome mining strategies for their prediction","authors":"Naveen Kumar,&nbsp;Prashant Bhagwat,&nbsp;Suren Singh,&nbsp;Santhosh Pillai","doi":"10.1016/j.biochi.2024.06.013","DOIUrl":"10.1016/j.biochi.2024.06.013","url":null,"abstract":"<div><div>Antibiotic resistance has become one of the most serious threats to human health in recent years. In response to the increasing microbial resistance to the antibiotics currently available, it is imperative to develop new antibiotics or explore new approaches to combat antibiotic resistance. Antimicrobial peptides (AMPs) have shown considerable promise in this regard, as the microbes develop low or no resistance against them. The discovery and development of AMPs still confront numerous obstacles such as finding a target, developing assays, and identifying hits and leads, which are time-consuming processes, making it difficult to reach the market. However, with the advent of genome mining, new antibiotics could be discovered efficiently using tools such as BAGEL, antiSMASH, RODEO, etc., providing hope for better treatment of diseases in the future. Computational methods used in genome mining automatically detect and annotate biosynthetic gene clusters in genomic data, making it a useful tool in natural product discovery. This review aims to shed light on the history, diversity, and mechanisms of action of AMPs and the data on new AMPs identified by traditional as well as genome mining strategies. It further substantiates the various phases of clinical trials for some AMPs, as well as an overview of genome mining databases and tools built expressly for AMP discovery. In light of the recent advancements, it is evident that targeted genome mining stands as a beacon of hope, offering immense potential to expedite the discovery of novel antimicrobials.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 99-115"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Boosting the antibacterial potential of a linear encrypted peptide in a Kunitz-type inhibitor (ApTI) through physicochemical-guided approaches 通过物理化学指导方法提高库尼茨型抑制剂(ApTI)中线性加密肽的抗菌潜力。
IF 3.3 3区 生物学
Biochimie Pub Date : 2024-12-01 DOI: 10.1016/j.biochi.2024.07.009
Camila de Oliveira Gutierrez , Luís Henrique de Oliveira Almeida , Janaina de Cássia Orlandi Sardi , Claudiane Vilharroel Almeida , Caio Fernando Ramalho de Oliveira , Reinaldo Marchetto , Edson Crusca , Danieli Fernanda Buccini , Octavio Luiz Franco , Marlon Henrique Cardoso , Maria Lígia Rodrigues Macedo
{"title":"Boosting the antibacterial potential of a linear encrypted peptide in a Kunitz-type inhibitor (ApTI) through physicochemical-guided approaches","authors":"Camila de Oliveira Gutierrez ,&nbsp;Luís Henrique de Oliveira Almeida ,&nbsp;Janaina de Cássia Orlandi Sardi ,&nbsp;Claudiane Vilharroel Almeida ,&nbsp;Caio Fernando Ramalho de Oliveira ,&nbsp;Reinaldo Marchetto ,&nbsp;Edson Crusca ,&nbsp;Danieli Fernanda Buccini ,&nbsp;Octavio Luiz Franco ,&nbsp;Marlon Henrique Cardoso ,&nbsp;Maria Lígia Rodrigues Macedo","doi":"10.1016/j.biochi.2024.07.009","DOIUrl":"10.1016/j.biochi.2024.07.009","url":null,"abstract":"<div><div>Bacterial resistance has become a serious public health problem in recent years, thus encouraging the search for new antimicrobial agents. Here, we report an antimicrobial peptide (AMP), called PEPAD, which was designed based on an encrypted peptide from a Kunitz-type plant peptidase inhibitor. PEPAD was capable of rapidly inhibiting and eliminating numerous bacterial species at micromolar concentrations (from 4μM to 10 μM), with direct membrane activity. It was also observed that the peptide can act synergistically with ciprofloxacin and showed no toxicity in the <em>G. mellonella in vivo</em> assay. Circular dichroism assays revealed that the peptide's secondary structure adopts different scaffolds depending on the environment in which it is inserted. In lipids mimicking bacterial cell membranes, PEPAD adopts a more stable α-helical structure, which is consistent with its membrane-associated mechanism of action. When in contact with lipids mimicking mammalian cells, PEPAD adopts a disordered structure, losing its function and suggesting cellular selectivity. Therefore, these findings make PEPAD a promising candidate for future antimicrobial therapies with low toxicity to the host.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 161-171"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","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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