International Journal of Peptide Research and Therapeutics最新文献

{"title":"Anti-Biofilm Effects of Melittin: Lessons Learned and the Path Ahead","authors":"Mojtaba Memariani, Hamed Memariani","doi":"10.1007/s10989-024-10606-w","DOIUrl":"https://doi.org/10.1007/s10989-024-10606-w","url":null,"abstract":"<p>Biofilm formation empowers microorganisms to withstand clearance mechanisms produced by host and synthetic sources. Biofilms are frequently held responsible for recurrent and chronic infectious diseases. Therefore, the development of effective anti-biofilm agents is of great importance. Melittin, the principal component in the venom of European honeybee, has sparked immense interest due to its anti-microbial, anti-cancer, anti-inflammatory, anti-diabetic, anti-neuropathic, wound-healing, and adjuvants properties. Considering the recent growth of research on the anti-biofilm effects of melittin, coupled with the absence of a dedicated review on this subject, the present review summarizes the key findings of the studies conducted thus far. Furthermore, this review offers several potentially fruitful areas for future research. Available evidence suggests that melittin can inhibit biofilm formation by important microbial pathogens such as <i>Acinetobacter baumannii</i>, <i>Borrelia burgdorferi</i>, <i>Enterococcus faecalis</i>, <i>Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Staphylococcus aureus</i>, <i>Streptococcus mutans</i>, and <i>Candida albicans.</i> The multifaceted mechanisms of melittin in combating biofilms are truly impressive, as it prevents microbial adhesion, inhibits biofilm development, downregulates genes crucial for biofilm formation and quorum-sensing pathways, disrupts the biofilm matrix, and eradicates biofilm-entrenched cells. Future investigations should prioritize the utilization of combination therapy with melittin and antibiotics, the implementation of advanced drug delivery systems, chemical modifications, and the conduction of in vivo studies using animal models.</p>","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Urotensin-II Prevents Cartilage Degeneration in a Monosodium Iodoacetate-Induced Rat Model of Osteoarthritis","authors":"Menderes Yusuf Terzi, Hamza Malik Okuyan, İhsan Karaboğa, Cemil Emre Gökdemir, Duygu Tap, Aydıner Kalacı","doi":"10.1007/s10989-024-10605-x","DOIUrl":"https://doi.org/10.1007/s10989-024-10605-x","url":null,"abstract":"","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JZTX-V, a Sodium Channel Inhibitor, Exhibits Excellent Analgesic Effects in Mouse Models","authors":"Chen Bo, Sun Zhenghua, Zeng Xiongzhi","doi":"10.1007/s10989-024-10603-z","DOIUrl":"https://doi.org/10.1007/s10989-024-10603-z","url":null,"abstract":"<p>JZTX-V, an inhibitor of voltage-gated sodium and potassium channels, is derived from the venom of the spider <i>Chilobrachys jingzhao</i> in China. JZTX-V was synthesized using a solid-phase chemical approach with Fmoc-protected amino acids to explore its function further. The synthetic peptides were purified using reverse-phase high-performance liquid chromatography (RP-HPLC) and then subjected to oxidative refolding under optimal conditions. A unique peak was observed in the RP-HPLC chromatogram for refolded JZTX-V, and the ratio to native JZTX-V was 1:1 for the mixed samples. Subsequently, the analgesic potential of the synthetic peptide was evaluated in mouse models of pain. In the Formarin model, JZTX-V significantly reduced pain scores in 60 min and its efficacy was comparable to that of morphine. JZTX-V also exhibited excellent analgesic effects in models of postoperative pain and mechanical allodynia. However, JZTX-V had no effect on thermal stimulation injury in the hot plate experiment and did not affect motor coordination. These results indicate that JZTX-V effectively alleviates inflammatory pain in animals and provides a promising template for the design of future clinical analgesic drugs.</p>","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naturally Occurring Imidazole Peptides, Carnosine and Anserine Inhibit the Degranulation of Mast Cells and Basophils by Modulating Intracellular Signaling","authors":"K. Yamaki, N. Kamiki, N. Nakatsuka, H. Yonezawa, A. Suzuki, S. Kubo, K. Ito, H. Fujisawa, Y. Koyama, K. Ohta, M. Ohta","doi":"10.1007/s10989-024-10604-y","DOIUrl":"https://doi.org/10.1007/s10989-024-10604-y","url":null,"abstract":"<p>Imidazole peptides possess multiple functions, including antioxidant effects, although their biological activities are largely unclear. Their production in humans and animals suggests their physiological roles and validates their safety for pharmaceutical or supplemental use. This study investigated the in vitro anti-anaphylactic potential of two histidine-containing dipeptides, carnosine and anserine in mast cells and basophils. Carnosine and anserine reduced mast cell degranulation elicited by anti-ovalbumin monoclonal IgE and ovalbumin or ionomycin in rat basophilic leukemia RBL2H3 cells without affecting cell viability. In contrast, interleukin-4 production following stimulation was enhanced in the presence of carnosine. Carnosine and anserine strongly inhibited Akt phosphorylation and moderately inhibited ERK phosphorylation. However, these peptides enhanced the increase in phosphorylated JNK levels upon IgE stimulation. The phosphorylation levels of p38 were not affected by carnosine or anserine. To determine the effect of carnosine on basophils, we established a method for detecting IgE-dependent activation in primary cultured mouse splenic basophils via CD63 expression for the first time. Carnosine treatment significantly reduced the increase in CD63 surface expression, a marker of degranulation, in mouse splenic basophils stimulated with anti-IgE. Flow cytometory analysis revealed that mean fluorescence intensities for non-stimulated, anti-IgE-stimulated, and carnosine-pre-treated/anti-IgE-stimulated basophils were 3853 ± 320, 5548 ± 282, and 3853 ± 203, respectively. The findings indicate carnosine and anserine suppress mast cell and basophil IgE-dependent degranulation. The proposed mechanism of the inhibitory effect is the suppression of the activation of phosphoinositide 3-kinase–Akt. Carnosine and anserine may exert anti-anaphylactic effects under physiological and pathological conditions and serve as safe potential drug candidates.</p>","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Characterization of Anticancer Peptides Derived from Snake Venom Metalloproteinase Library","authors":"S. Saranya, M. Bharathi, N. Senthil Kumar, P Chellapandi","doi":"10.1007/s10989-024-10602-0","DOIUrl":"https://doi.org/10.1007/s10989-024-10602-0","url":null,"abstract":"<p>Snake venom metalloproteinases (SVMPs) are enzymatic proteins found in snake venom and are known for their diverse biological activities, including induction of hemorrhage and degradation of fibrinogen. This study aimed to design and characterize anticancer peptides (ACPs) derived from an SVMP library based on their physicochemical properties. A comprehensive analysis predicted 185 ACPs and 177 non-ACPs from 652 SVMPs using a SVM algorithm. Among these, only 23 ACPs demonstrated the ability to penetrate cell membranes, of which 5 were selected as promising candidates. A reliable SVM and confidence scores were obtained for all ACP predictions. The predicted ACPs showed optimal hydrophobicity and favorable structural stability in plasma. The predicted ACPs were characterized by low solubility, high rigidity, and high interaction potential based on their net charge, net hydrogen, and steric hindrance. Among the five ACPs, ACP1 (GDLAAIRKRV) and ACP3 (GDETEIRSRI) had unique amino acid compositions, specifically arginine, lysine, aspartic acid, glutamic acid, and α-helical structures. Molecular docking simulations indicated their interactions with various cancer target proteins, leading to inhibit tumor cell proliferation or migration. In conclusion, ACP01 and ACP03 are potential candidates for the future treatment of breast cancer and leukemia.</p>","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140311337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in silico Evaluation of the Anti-Biofilm Activity of Histatin 5 against Streptococcus mutans","authors":"Shiva Golshani, Aida Iraji, Zeinab Kadkhoda, Alireza Vatanara","doi":"10.1007/s10989-024-10601-1","DOIUrl":"https://doi.org/10.1007/s10989-024-10601-1","url":null,"abstract":"<p>Dental caries is a prevalent and costly disease throughout the world. <i>Streptococcus mutans</i> is widely recognized as one of the key contributing factors in the development of dental caries. Major virulence factors associated with the cariogenicity of <i>S. mutans</i> include adhesion, formation biofilm, acidogenicity and acidurity. Histatin 5, a salivary antimicrobial peptide, exhibited therapeutic effects in the oral cavity. The aim of this study was to evaluate the potential anti-biofilm effects of histatin 5 against <i>S. mutans</i> via in vitro and <i>in silico</i> approaches. Also, the impact of histatin 5 on acidogenicity and acidurity was accessed. The resazurin microdilution method was used to evaluate the anti-biofilm and anti-adhesive activity. Furthermore, molecular docking was carried out to identify the crucial structural features of histatin 5 in binding to glucansucrase enzyme of <i>S. mutans</i>, which is involved in biofilm formation. The findings showed that histatin 5 considerably inhibited the biofilm formation of <i>S. mutans</i> in a dose-dependent manner and could potentially limit the acidogenicity and acidurity of <i>S. mutans</i>. The results of confocal laser scanning microscopy indicated the inhibitory effects of histatin 5 on biofilm formation of <i>S. mutans</i> cells. Moreover, histatin 5 displayed a favorable interaction with glucansucrase, which suggests that it could potentially act as an inhibitor for this enzyme. These findings suggest that histatin 5 could be a promising candidate for the development of a new efficient therapeutic agent for the prevention and treatment of dental caries.</p>","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140298746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Antiviral Activity of Two Host Defense Peptides Against Human alphaherpesvirus 1","authors":"Gisele Regina Rodrigues, Rhayfa Lorrayne Araujo Berlanda, Liana Costa Pereira Vilas Boas, Lídia Maria Pinto de Lima, Octávio Luiz Franco","doi":"10.1007/s10989-024-10597-8","DOIUrl":"https://doi.org/10.1007/s10989-024-10597-8","url":null,"abstract":"<p>Viral infections are continually emerging with new characteristics and the potential to cause outbreaks or pandemics. Therefore, identification of new antiviral compounds is extremely necessary for therapeutic. This study aimed to evaluate the in vitro action of host defense peptides against <i>Human alphaherpesvirus 1</i> (HHV-1) replication. Vero cell monolayers were infected with HHV-1 TCID₅₀ and treated with different concentrations of IDR-1018 and DJK-6. The cell viability was evaluated by MTT method. Time of addition assays were performed to infer the effect of peptides upon the viral replicative cycle. IDR-1018 and DJK-6 were able to inhibit the HHV-1 replication in maximum nontoxic concentrations. However, IDR-1018 presented higher potency and a better safety profile. In addition, IDR-1018 probably inhibits adhesion, entry and post entry of virus infection. DJK-6 seems to be capable of interfering with virus entry and viral biosynthesis.</p>","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140168199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apelin is Peptide Increasing Tolerance of Organs and Cells to Hypoxia and Reoxygenation. The Signaling Mechanism","authors":"Sergey Valentinovich Popov, Leonid Nikolaevich Maslov, Alexandr Valerievich Mukhomedzyanov, Maria Sirotina, Natalia Vladimirovna Naryzhnaya, Boris Konstantinovich Kurbatov, Alexandr Sergeevich Gorbunov, Michail Kilin, Viacheslav Nikolaevich Azev, Nirmal Singh, Feng Fu, Jian-Ming Pei","doi":"10.1007/s10989-024-10599-6","DOIUrl":"https://doi.org/10.1007/s10989-024-10599-6","url":null,"abstract":"<p>Over the last three decades, treatment of stroke and acute myocardial infarction (AMI) has been improved, but it has stagnated in the last few years. Patients with stroke and AMI are admitted with formed ischemic injury of the brain or the heart, thereby it is difficult to affect this injury. However, it was possible to affect reperfusion injury of the brain or the heart. Ischemic damage to the lung is observed in pulmonary embolism. Ischemia and reperfusion of kidneys are observed in kidney transplantation. Significant progress in an increase in the efficacy of kidney transplantation, in treatment of stroke, pulmonary embolism, and AMI can be achieved through the development of novel drugs capable of preventing reperfusion injury of the brain or the heart with high efficiency. Synthetic apelin analogues with a long half-life could be prototypes of such drugs. It was found that apelins can increase tolerance of the heart, the brain, the lung, and the intestine to ischemia/reperfusion (I/R). Protein kinases are involved in the neuroprotective, cardioprotective, renoprotective, and pulmonoprotective effects of apelins. Mitochondrial permeability transition pore and ATP-sensitive K⁺ channels are also involved in the protective effects of apelins. Apelins inhibit apoptosis and ferroptosis. Apelins activate autophagy of cardiomyocytes. Enzyme-resistant apelin analogues are perspective peptides for treatment of AMI, stroke, and I/R injury of lungs and kidneys.</p>","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140148680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Anti-biofilm Efficacy of Kyotorphin Derivatives and Biosafety Assessment: In Vitro and In Vivo Investigations Targeting Bacterial and Fungal Pathogens","authors":"Isabel Chaves Silva Carvalho, Fernanda da Silva Seiffert Simões, Vitor Martins de Andrade, Dayane Batista Tada, Montserrat Heras, Eduard Bardají, Mônica Lopes Ferreira, Miguel Augusto Rico Botas Castanho, Katia Conceição","doi":"10.1007/s10989-024-10598-7","DOIUrl":"https://doi.org/10.1007/s10989-024-10598-7","url":null,"abstract":"<p>Kyotorphin (KTP) dipeptide (<span>l</span>-Tyrosine-<span>l</span>-Arginine) and their derivatives possess a multitude of functions, qualifying them as \"multifunctional peptides.\" Considering the escalating bacterial resistance to antibiotics, antimicrobial peptides offer a promising road, forming the central focus of this current investigation. The effectiveness of KTP derivatives, GABA-KTP-NH₂ and Indol-KTP-NH₂, were assessed for biofilm inhibition in bacterial and fungal strains. The viability of these derivatives was tested in fibroblasts and B16-F10-Nex2 cells. In vivo toxicity was evaluated using the model organisms <i>Galleria mellonella</i> and <i>Danio rerio</i>. Notably, both GABA-KTP-NH₂ and Indol-KTP-NH₂ derivatives effectively hindered biofilm formation in <i>E. coli</i>, <i>S. pneumoniae</i>, and <i>C. krusei</i>. In the <i>G. mellonella</i> model, the derivatives exhibited significant larval survival rates in toxicity tests, while in infection tests, they demonstrated efficient treatment against the evaluated microorganisms. Conversely, zebrafish assays revealed that Indol-KTP-NH₂ induced substantial mortality rates in embryos after 72 and 96 h of exposure. Similarly, the GABA-KTP-NH₂ derivative exhibited heightened lethality, noticeable at the 100 μM concentration after the same exposure periods. Importantly, toxicity assessments unveiled a relatively lower toxicity profile, coupled with a reduced potential for inducing abnormalities. These results highlight the necessity of employing a comprehensive approach that integrates diverse techniques to thoroughly assess toxicity implications.</p>","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands","authors":"Yu Du, Lin Xu","doi":"10.1007/s10989-024-10596-9","DOIUrl":"https://doi.org/10.1007/s10989-024-10596-9","url":null,"abstract":"<p>Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with <i>π</i>-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation.\u0000</p>","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}