Protein and Peptide Letters最新文献

{"title":"Recombinant Production of Ib-AMP₄ and Oncorhyncin II Antimicrobial Peptides and Antimicrobial Synergistic Assessment on the Treatment of <i>Staphylococcus aureus</i> Under <i>In vitro</i> Condition.","authors":"Majid Safari, Hamid Abtahi, Shima Chehreii, Shohreh Fahimirad","doi":"10.2174/0109298665327474241112093601","DOIUrl":"10.2174/0109298665327474241112093601","url":null,"abstract":"<p><strong>Background: </strong>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a significant and prevalent pathogen that poses a major challenge in healthcare environments. In light of the growing threat posed by multidrug-resistant organisms like MRSA, there is an urgent need for alternative therapeutic strategies. One promising avenue of research involves the use of antimicrobial peptides (AMPs). These naturally occurring molecules, which are part of the innate immune response in many organisms, have garnered attention for their ability to combat a wide range of pathogens.</p><p><strong>Objectives: </strong>This study aimed to produce recombinant versions of Ib-AMP₄ and Oncorhyncin II and to evaluate their combined effects against MRSA (NCTC10442).</p><p><strong>Methods: </strong><i>Escherichia coli BL21(DE₃)</i> served as the expression host for the synthesized variants of the Ib-AMP₄ and Oncorhyncin II genes. The antimicrobial efficacy of these peptides against MRSA <i>S. aureus</i> (NCTC1042) was evaluated using a comprehensive methodology that encompassed the determination of the minimum inhibitory concentration (MIC), the performance of time-kill assays, and the analysis of growth kinetics.</p><p><strong>Results: </strong>The individual antimicrobial activities of Ib-AMP₄ and Oncorhyncin II were assessed, revealing minimum inhibitory concentrations (MICs) of 27.75 μg/mL and 40.125 μg/mL against S. aureus (MRSA) (NCTC10442), respectively. The application of a checkerboard assay to evaluate the combination of these antimicrobial peptides (AMPs) demonstrated a synergistic interaction, which was further validated through time-kill and growth kinetic studies. When administered at double the MIC, a significant reduction in the log₁₀ CFU/mL of MRSA (NCTC 10442) was observed, underscoring the synergistic bacteriostatic effect mediated by the fractional inhibitory concentration (FIC) index of the two peptides.</p><p><strong>Conclusion: </strong>Antimicrobial peptides (AMPs) have attracted significant interest owing to the growing intricacy of microbial infections. They constitute a promising category of novel antibiotics that warrant further investigation for the treatment of <i>S. aureus</i> infections and the enhancement of wound healing. Although certain AMPs can operate autonomously, others may necessitate a synergistic approach alongside conventional antibiotics. Studies examining the combined efficacy of Oncorhyncin II and Ib-AMP₄ against MRSA <i>in vitro</i> have revealed their effectiveness.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"34-43"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732170","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":"Amphibian-Derived Antimicrobial Peptides: Essential Components of Innate Immunity and Potential Leads for New Antibiotic Development.","authors":"Ebru Tanriverdi O","doi":"10.2174/0109298665356946241218103145","DOIUrl":"10.2174/0109298665356946241218103145","url":null,"abstract":"<p><p>Like other vertebrates, amphibians possess innate and adaptive immune systems. At the center of the adaptive immune system is the Major Histocompatibility Complex. The important molecules of innate immunity are antimicrobial peptides (AMPs). These peptides are secreted by granular glands in the skin and protect the animal against microorganisms entering its body through the skin. AMPs offer an effective and rapid defense against pathogenic microorganisms and have cationic and amphiphilic structures. These peptides are small gene-encoded molecules of 8-50 amino acid residues synthesized by ribosomes. These small molecules typically exhibit activity against bacteria, viruses, fungi, and even cancer cells. It is known that today's amphibian AMPs originated from a common precursor gene 150 million years ago and that the origin of these peptides is preprodermaseptins. Today, antibiotic resistance has occurred due to the incorrect use of antibiotics. Traditional antibiotics are becoming increasingly inadequate. AMPs are considered promising candidates for the development of new-generation antibiotics. Therefore, new antibiotic discoveries are needed. AMPs are suitable molecules for new-generation antibiotics that are both fast and have different killing mechanisms. One of the biggest problems in the clinical applications of AMPs is their poor stability. AMPs generally have limited tropical applications because they are sensitive to protease degradation. Coating these peptides with nanomaterials to make them more stable can solve this problem.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"97-110"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953978","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":"ZNF165: A Pan-Cancer Biomarker with Prognostic and Therapeutic Potential.","authors":"Guizhen Lyu, Dongbing Li","doi":"10.2174/0109298665351592250106062250","DOIUrl":"10.2174/0109298665351592250106062250","url":null,"abstract":"<p><strong>Background: </strong>The role of ZNF165 in only a few tumors has been reported. ZNF165 plays an important role in liver cancer, gastric cancer, and breast cancer, especially in regulating the immune microenvironment, promoting tumor cell proliferation and migration, and serving as a potential target for immunotherapy.</p><p><strong>Objective: </strong>This study aimed to enhance an understanding of how the ZNF165 gene functions and influences cancer development.</p><p><strong>Methods: </strong>Using a suite of online resources, including TIMER, TCGA, GTEx, GEPIA2, cBioPortal, TIMER2, STRING, DAVID, RNAactDrug, CancerSEA, and UCSC, along with comprehensive statistical analyses, we conducted a thorough investigation of the pan-cancer landscape of ZNF165. This study encompassed an assessment of ZNF165 levels, their associations with patient outcomes, and clinical correlates. We examined the interplay between ZNF165 and key cancer biomarkers, such as Microsatellite Instability (MSI), Tumor Mutational Burden (TMB), immune cell infiltration, and the expression of immune checkpoint genes. We delved into the genetic variations of ZNF165, its biological roles across various cancer types, and its potential links to drug responsiveness. We analyzed single-cell expression patterns of ZNF165 and their implications for the functional dynamics of cancer. We employed quantitative Reverse Transcription PCR (qRT-PCR) to measure ZNF165 levels in Ovarian Cancer (OC) cell lines.</p><p><strong>Results: </strong>ZNF165 expression displayed aberrations across a diverse range of human cancers and exhibited correlations with clinical stages. High ZNF165 expression in KIRC, KIRP, STAD, and UCEC was significantly associated with poor overall survival. ZNF165 has encouraging diagnostic value in specific tumor types, with gene amplification identified as the predominant genetic alteration. Our analysis further uncovered significant associations between ZNF165 levels and MSI across three distinct cancer types, as well as with TMB in six different malignancies. We detected substantial correlations between ZNF165 levels and immune cell infiltration, as well as the expression of immune checkpoint genes. ZNF165 was found to be involved in several prevalent signaling pathways across various cancer types. ZNF165 may potentially contribute to chemotherapy and chemoresistance, and was observed to be involved in cancer progression. A ceRNA regulatory network involving AFDN-DT, miR-191-5p, and ZNF165 was constructed for OC, revealing significantly elevated ZNF165 levels in OC cell lines. Dysregulated ZNF165 expression across a spectrum of malignancies might play a role in cancer initiation and advancement via multiple biological pathways.</p><p><strong>Conclusion: </strong>ZNF165 may serve as a promising therapeutic target for the treatment of cancer in human patients.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"206-223"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047661","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":"Virtual Screening of Phytoconstituents in Indian Spices based on their Inhibitory Potential against SARS-CoV-2.","authors":"Vaishali Singh, Aliza Rabbani, Veda P Pandey","doi":"10.2174/0109298665366911250416113831","DOIUrl":"10.2174/0109298665366911250416113831","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly pathogenic human coronavirus (CoV). For the treatment of COVID-19, various drugs, ayurvedic formulations, used for other diseases, were repurposed. Ayurveda and yoga exhibited a pivotal role in the treatment of COVID-19. Various medicinal plants, including garlic, tulsi, clove, cinnamon, ginger, black pepper, and turmeric, are recommended for the prevention of COVID-19 as immunity boosters along with their antiviral property.</p><p><strong>Objective: </strong>In view of the drug repurposing approach, the present work has been initiated with the broader objectives of screening and identification of phytoconstituents of Indian spices against targets, namely furin, 3C-like protease (3CL-PRO), NSP-9 RNA binding protein, papain-like protease, RNA dependent RNA polymerase (RDRP), spike protein concerned with life cycle of SARS-CoV-2 using in-silico tools.</p><p><strong>Methods: </strong>The phytoconstituents of Indian spices were screened for interaction with several targets using a molecular docking approach with the help of Discovery Studio 4.5 software. Furthermore, the pharmacokinetic analyses of selected ligands using ADMET and Lipinski's rule of five were also performed.</p><p><strong>Results: </strong>In the present study, a total of 37 active phytoconstituents of Indian spices were screened for interaction with several identified targets of COVID-19 using a molecular docking approach. The ligands, namely morin, gingerol, myristic acid, quercetin, gallic acid and alliin were found to be the top interacting ligands with the targets analyzed.</p><p><strong>Conclusion: </strong>Based on the present <i>in-silico</i> finding, the active components of spices could be considered for drug-lead compounds against COVID-19.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"335-352"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008456","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":"A Review on the Potential Role of Humanin Peptide and its Analogs in the Regulation of Autophagy Pathways for Therapeutic Application in Metabolic Disorders.","authors":"Hira Moin, Rizwan Ashraf, Batool Butt, Imtiaz Mustafa, Mamoona Shafiq, Syed Ali Raza Shah","doi":"10.2174/0109298665363711250112050930","DOIUrl":"10.2174/0109298665363711250112050930","url":null,"abstract":"<p><p>Autophagy is a self-eating cellular process in which the cell breaks down worn-out organelles, damaged/defective proteins, and toxins. Impaired autophagy is a significant factor in the development of various metabolic disorders, along with oxidative stress, inflammation, mitochondrial and endoplasmic reticulum dysfunction. These disorders pose a significant health and economic burden on the global human population, owing to their steadily rising prevalence. Therefore, modulating the expression of proteins involved in the autophagy-related pathways can be a promising avenue for curbing the development and progression of these disorders. Humanin (HN) is a 24-amino acid mitochondrial-derived peptide. It possesses anti-oxidant, anti-inflammatory, and pro-apoptotic properties. The analogs of HN can be generated by replacing specific amino acids in the polypeptide chain, thereby functionally modifying the peptide. Among these, humanin- glycine (HNG) is the most widely studied analog in both <i>in vivo</i> and <i>in vitro</i> disease models. It is far more potent than HN, with a potency that is 1000 times greater. To the best of our knowledge, this review is the first to discuss and examine the available evidence regarding the potential involvement of HN or its analogs in regulating autophagy pathways. The review primarily highlights that HN is an autophagy inducer, which can promote cell survival in the presence of metabolic and oxidative stress, particularly the HNG analog. Future research is imperative to comprehensively evaluate the effects of HN and its analogs on autophagy. Further investigations are needed to correlate its levels with various autophagic markers in different metabolic diseases, offering the potential for groundbreaking discoveries in understanding disease mechanisms and developing novel therapeutic strategies.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"161-170"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415052","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":"Exploring the Regulatory Interaction of Differentially Expressed Proteins in Cleft Palate Induced by Retinoic Acid.","authors":"Liyun Chen, Aiwei Ma, Lewen Jiang, Jufeng Fan, Wenshi Jiang, Mengjing Xu, Xujue Bai, Jianda Zhou, Wancong Zhang, Shijie Tang","doi":"10.2174/0109298665308502240820115618","DOIUrl":"10.2174/0109298665308502240820115618","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to identify novel proteins involved in retinoic acid (RA)-induced embryonic cleft palate development.</p><p><strong>Methods: </strong>The palate tissues of the control and RA-treated E14.5 were dissected and subjected to iTRAQ-based proteomic analysis.</p><p><strong>Results: </strong>Differential expression analysis identified 196 significantly upregulated and 149 downregulated considerably proteins in RA-induced palate tissues. Comprehensive Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed the significant involvement of cytoplasmic translation, ribosome biogenesis, glycolysis/gluconeogenesis, and glutathione metabolism pathways in cleft palate pathogenesis triggered by RA. In particular, ribosome-related pathways were highly enriched, while glycolysis was disrupted. Protein-protein interaction analysis, facilitated by the STRING database, revealed a tightly interconnected network of differentially expressed proteins. Further analysis using the cytoHubba plugin in Cytoscape identified ten hub proteins, including Eif4a1, Gapdh, Eno1, Imp3, Rps20, Rps27a, Eef2, Hsp90ab1, Rpl19, and Rps16, indicating their potential roles in RA-induced cleft palate development, and thus positioning them as potential biomarkers for cleft palate.</p><p><strong>Conclusion: </strong>These findings provide valuable insights into the proteomic changes associated with RA-induced cleft palate and shed light on key pathways and proteins that can contribute significantly to the pathogenesis of this congenital condition.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"54-61"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547006","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":"Exploring New Structures of Kinase Inhibitors and Multitarget Strategies in Alzheimer's Disease Treatment.","authors":"Siddhant Tripathi, Yashika Sharma, Dileep Kumar","doi":"10.2174/0109298665348075241121071614","DOIUrl":"10.2174/0109298665348075241121071614","url":null,"abstract":"<p><p>Alzheimer's disease (AD) treatments currently available have ineffective results. Previously employed Acetylcholine esterase inhibitors and memantine, an NMDA receptor antagonist, target a single target structure that plays a complex role in the multifactorial progression of disease. Memantine moderates the toxic effects of excessive glutamate activity by blocking NMDA receptors, which decreases neurotoxicity in AD, while acetylcholine esterase inhibitors function by blocking cholinergic receptors (muscarinic and nicotinic), preventing the breakdown of acetylcholine, thereby enhancing cholinergic transmission, thus improving cognitive functions in mild to moderate stages of AD. Every drug class targets a distinct facet of the intricate pathophysiology of AD, indicating the diverse strategy required to counteract the advancement of this neurodegenerative disorder. Thus, patients are currently not getting much benefit from current drugs. A closer look at the course of AD revealed several potential target structures for future drug discovery. AD drug development strategies focus on developing new target structures in addition to well-established ones for combination treatment regimens, ideally with a single drug that can target two different target structures. Because of their roles in AD progression pathways like pathologic tau protein phosphorylations as well as amyloid β toxicity, protein kinases have been identified as potential targets. This review will give a quick rundown of the first inhibitors of single protein kinases, such as glycogen synthase kinase (gsk3) β, along with cyclin-dependent kinase 5. We will also look into novel inhibitors that target recently identified protein kinases in Alzheimer's disease, such as dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Additionally, multitargeting inhibitors, which target multiple protein kinases as well as those thought to be involved in other processes related to AD will be discussed. This kind of multitargeting offers prospective hope for improved patient outcomes down the road since it is the most effective way to impede multifactorial disease development.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"2-17"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882794","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":"ZP3 Expression in Pancreatic Adenocarcinoma: Its Implications for the Prognosis and Therapy.","authors":"Guizhen Lyu, Dongbing Li","doi":"10.2174/0109298665350171241204153202","DOIUrl":"10.2174/0109298665350171241204153202","url":null,"abstract":"<p><strong>Background: </strong>The role of Zona pellucida glycoprotein 3 (ZP3) is unclear in pancreatic adenocarcinoma (PAAD).</p><p><strong>Objective: </strong>This study aimed to explore the role of ZP3 in PAAD.</p><p><strong>Methods: </strong>A comparative analysis of ZP3 gene expression was performed to discern differences between various types of cancer and PAAD, leveraging data sourced from The Cancer Genome Atlas (TCGA). This study aimed to assess the role of ZP3 as a potential diagnostic marker for PAAD. The relationship between ZP3 levels and clinical characteristics, as well as patient outcomes, was scrutinized. Additionally, genomic enrichment analysis was carried out to uncover the underlying regulatory mechanisms associated with ZP3. The study further delved into the association of ZP3 with immune system interactions, checkpoint gene expression, Tumor Mutational Burden (TMB), microsatellite instability (MSI), and tumor stemness index (mRNAsi). The aberrant expression patterns of ZP3 in PAAD cell cultures were confirmed through the application of quantitative reverse transcription PCR (qRT-PCR) techniques.</p><p><strong>Results: </strong>ZP3 exhibited aberrant expression in both pan-cancer and PAAD. A significant correlation was observed between increased levels of ZP3 expression in PAAD patients and histologic grade (p = 0.026). Elevated ZP3 expression in PAAD was found to be significantly associated with poorer overall survival (p = 0.003), progression-free survival (p = 0.012), and disease-specific survival (p = 0.002). In PAAD, the level of ZP3 gene expression was statistically significant (p < 0.001) and recognized as a key determinant of patient prognosis. ZP3 exhibited associations with various biological pathways, including primary immunodeficiency, oxidative phosphorylation, and other pathways. ZP3 expression demonstrated correlations with immune infiltration, immune checkpoint genes, TMB, MSI, and mRNAsi in PAAD. Moreover, a pronounced negative correlation was detected between ZP3 expression levels and the therapeutic effectiveness of various medications, including selumetinib, bleomycin, FH535, docetaxel, and tanespimycin, within the context of PAAD. Elevated levels of ZP3 were consistently observed in cell line models of PAAD.</p><p><strong>Conclusion: </strong>ZP3 has the potential to serve as a prognostic biomarker and therapeutic target for patients with PAAD.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"124-138"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953980","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":"Clay-Polymer Nanocomposites Mediated Inhibition of Protein Aggregation: Possible Role in the Prevention of Proteinopathies.","authors":"Romana Parveen, Sher Ali, Sadaf Fatima","doi":"10.2174/0109298665274059231002071951","DOIUrl":"10.2174/0109298665274059231002071951","url":null,"abstract":"<p><strong>Background: </strong>The transformation of proteins from their native conformation into highly ordered fibrillar structures due to their misfolding and aggregation under particular conditions are described as beta-sheet enriched amyloid fibrils. The accumulation of these fibrils in different body parts is the major cause of several neurological and non-neurological conditions (proteinopathies).</p><p><strong>Objectives: </strong>To prevent these proteinopathies, inhibition of protein aggregation is considered a promising strategy. Therefore, in this study, we synthesized montmorillonite (MMT) based poly- orthophenylenediamine (PoPD) nanocomposites (NCs) and characterized their size and morphology due to their remarkable biological properties. Further, the effect of these nanocomposites on inhibition of fibril formation was assessed.</p><p><strong>Methods: </strong>These nanocomposites were evaluated for their anti-amyloidogenic potential on two model proteins of amyloidopathies, i.e., human lysozyme and human serum albumin (HL & HSA), by using several biophysical methods, such as Thioflavin T (ThT) and 1-anilino-8-naphthalene sulfonate (ANS) fluorescence, congo red dye binding assay (CR). Secondary structural content was evaluated by Circular dichroism (CD) spectroscopy.</p><p><strong>Results: </strong>Results demonstrated that synthesized nanocomposites significantly inhibited fibril formation in dose-dependent manner that corresponds to their ability to arrest fibrillation. It is suggested that they may adsorb proteins to protect them against aggregation when they are subjected to aggregating conditions.</p><p><strong>Conclusion: </strong>This study offers an opportunity to understand the mechanism of inhibition of fibril formation by nanocomposites, showing that they inhibit amyloid formation and amyloid diseases. Thus, the study concludes that these nanocomposites are promising candidates as therapeutic molecules for proteinopathies and are envisaged to enrich the area of personalized medicine, augmenting the human healthcare system.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"139-151"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49681633","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":"Identifying the Role of Individual Seal IAPP Amino Acids in Inhibiting the Aggregation of Human IAPP.","authors":"Kate Menefee, Kelsy Larios, Dillon J Rinauro, Angela Tun, Betssy Jauregui, Jessica I Contreras, Luiza A Nogaj, David A Moffet","doi":"10.2174/0109298665340227241115110404","DOIUrl":"10.2174/0109298665340227241115110404","url":null,"abstract":"<p><strong>Introduction: </strong>The progression of type 2 diabetes in humans appears to be linked to the loss of insulin-producing β-cells. One of the major contributors to β-cell loss is the formation of toxic human IAPP amyloid (hIAPP, Islet Amyloid Polypeptide, amylin) in the pancreas. Inhibiting the formation of toxic hIAPP amyloid could slow, if not prevent altogether, the progression of type 2 diabetes. Many non-human organisms also express amyloidogenic IAPP variants known to kill pancreatic cells and give rise to diabetes-like symptoms. Surprisingly, some of these non-human IAPP variants function as inhibitors of hIAPP aggregation, raising the possibility of developing non-human IAPP peptides into anti-diabetic therapeutic peptides. One such inhibitory IAPP variant is seal IAPP, which has been shown to inhibit hIAPP aggregation. Seal IAPP only differs from hIAPP by three amino acids. In this study, each of the six seal/human IAPP permutations was analyzed to identify the role of each of the three amino acid positions in inhibiting hIAPP aggregation.</p><p><strong>Aims: </strong>This study aimed to identify the minimal amino acid substitutions to yield a peptide inhibitor of human IAPP aggregation.</p><p><strong>Objective: </strong>The goal of the study was to determine the minimal amino acid substitutions necessary to convert human IAPP into an amyloid-inhibiting peptide.</p><p><strong>Methods: </strong>The formation of toxic hIAPP amyloid was monitored using Thioflavin T binding assays, atomic force microscopy, and MTT cell rescue studies.</p><p><strong>Results: </strong>One seal IAPP variant retained amyloid-inhibition activity, and two variants appeared to be more amyloidogenic and toxic than wild-type human IAPP.</p><p><strong>Conclusion: </strong>These results suggest that inhibition of hIAPP requires both the H18R and F23L substitutions of hIAPP.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"44-53"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807520","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}