Protein and Peptide Letters最新文献

{"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}

{"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":"iRGD Tumor Penetrating Peptide-Modified NK Cells Exhibit Enhanced Tumor Immune Infiltration Ability and Anti-Tumor Efficacy.","authors":"Ge Song, Xueyong Qi, Yi Zhao","doi":"10.2174/0109298665348639250115113650","DOIUrl":"10.2174/0109298665348639250115113650","url":null,"abstract":"<p><strong>Background: </strong>Natural killer (NK) cells, as part of the group I innate lymphocytes (ILCs) are essential for tumor immune surveillance. NK cells can recognize and eliminate target cells without the need for prior sensitization or restriction of major histocompatibility complexes (MHCs) and antigens. However, the limited infiltration of metastatic NK cells poses significant challenges for advancing adoptive cell immunotherapy for solid tumors.</p><p><strong>Objective: </strong>This study aimed to explore the potential of using tumor penetrating peptide (TPP) iRGD to promote the delivery of activated NK cells to deeper layers of tumor tissue.</p><p><strong>Methods: </strong>Flow cytometry was performed to evaluate the activation, inhibition, and expression of other receptors involved in cytotoxicity. High-pressure liquid chromatography (HPLC) and mass spectrometry were used to detect the purity of iRGD. 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-poly(ethylene glycol)-iRGD (DSPE-PEG-iRGD) was synthesized. Surface modification of cells was performed using DSPE-PEG-iRGD. Multicellular tumor spheroids (MCTSs) were established to evaluate permeability. In addition, in order to better simulate the physiological characteristics of solid tumors in vivo, we generated 3D spheroids from HGC27 gastric cancer cell line and BXPC-3 pancreatic cancer cell line to study the anti-tumor effect of NK cells with combination iRGD <i>in vitro</i>. The mouse models of gastric cancer and pancreatic cancer were used. In addition, the synergistic anti-tumor effects were evaluated <i>in vivo</i> based on the tumor volume and body weight of mice.</p><p><strong>Results: </strong>Initially, we treated NK cells with interleukin-2 (IL-2), resulting in significant activation as indicated by upregulation of CD56. On the 15th day, the proliferation of CD3-/56+cell population in NK cell culture containing IL-2 significantly increased, and the NK cell amplification factor was greater than 300. In addition, NK cells exhibited increased cytotoxicity towards cancer cell lines. When the ratio of effect to target was 10:1, the killing rate of NK cells against BXPC-3 was 83.1%. iRGD modification enabled NK cells to penetrate MCTSs, resulting in cytotoxicity against target HGC27 and BXPC-3 cells. In addition, NK cells modified with iRGD significantly reduced tumor growth in the xenotransplantation model of gastric cancer and pancreatic cancer mice model.</p><p><strong>Conclusion: </strong>In summary, our results indicated that NK cells exhibited higher efficacy and lifespan against cancer cell lines in vitro. Furthermore, the integration of iRGD into NK cells led to improved infiltration and targeted elimination of MCTSs. Moreover, the application of iRGDmodified NK cells has shown significant anti-tumor efficacy against solid tumors in vivo. This joint strategy may significantly improve the efficacy of NK cell immunotherapy in treating various solid tumors.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"183-193"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin/Melanocortin Pathway in Cholelithiasis Patients: A Diagnostic Perspective.","authors":"Tugba Agbektas, Gulsen Guclu, Ayca Tas, Esma Ozmen, Omer Topcu, Suleyman Aydin, Yavuz Silig","doi":"10.2174/0109298665343979241025114114","DOIUrl":"10.2174/0109298665343979241025114114","url":null,"abstract":"<p><strong>Background: </strong>Cholelithiasis is the most prevalent inflammatory condition of the gallbladder. The regulation of biological processes, including energy homeostasis, and control of body weight are key mechanisms that the leptin and melanocortin pathways play a role in Cholelithiasis is the most prevalent inflammatory condition of the gallbladder. There are various risk factors for the development of gallstone disease, especially weight gain, and obesity is just one of them. This risk factor can be minimized by maintaining appetite and energy balance. Here, leptin and melanocortin pathways are the key mechanisms in maintaining appetite and energy homeostasis.</p><p><strong>Objectives: </strong>The aim of this study was to investigate the relationship between the levels of LEP, LEPR, TrkB, BDNF, POMC, and MC4R proteins in patients with Cholelithiasis. This study aims to determine the relationship between LEP, LEPR, TrkB, BDNF, POMC, and MC4R protein levels, which play a role in maintaining appetite and energy homeostasis, and cholelithiasis.</p><p><strong>Methods: </strong>This study examined 44 patients diagnosed with Cholelithiasis and 44 healthy control subjects who had not previously been diagnosed with any form of Cholelithiasis. The levels of leptin (LEP), Leptin Binds To Leptin Receptors (LEPR), Tropomyosin Receptor Kinase B (TrkB), Brain-Derived Neurotrophic Factor (BDNF), Pro-OpioMelanoCortin (POMC), and Melanocortin- 4 Receptors (MC4R) molecules were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The results were analyzed using the SPSS Software (Version 22.0) program and GraphPad Prism 8.0.1 software.</p><p><strong>Results: </strong>The study found a statistically significant decrease (p < 0.05) in MC4R, TrkB, BDNF, and POMC protein levels in Cholelithiasis patients compared to the control group. There was no statistically significant difference in LEP and LEPR concentration values between the two groups (p = 0.247, p = 0.674).</p><p><strong>Conclusion: </strong>The proteins MC4R, TrkB, BDNF, and POMC, which are involved in the leptin and melanocortin pathways may play a significant role in Cholelithiasis disease. However, more detailed research on the relevant proteins is needed. Nevertheless, this research will guide new studies.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"75-83"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710916","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":"Structural and Functional Insights into UDGs.","authors":"Shreya Roy, Md Khabeer Azhar, Vibha Gupta","doi":"10.2174/0109298665318621241128041145","DOIUrl":"10.2174/0109298665318621241128041145","url":null,"abstract":"<p><p>Endogenous or exogenous DNA damage needs to be repaired, therefore, cells in all the three domains have repair pathways to maintain the integrity of their genetic material. Uracil DNA glycosylases (UDGs), also known as UNGs (uracil-DNA N-glycosylases), are part of the base-excision repair (BER) pathway. These enzymes specifically remove uracil from DNA molecules by cleaving the glycosidic bond between the uracil base and the deoxyribose sugar. UDGs can be broadly classified into six families, and each of them share conserved motifs that are critical for substrate recognition and catalysis. Recently, an unconventional UDG known as UDGX has been identified from the species <i>Mycobacterium smegmatis</i>, which is different from other UDG members in forming an irreversible and extremely stable complex with DNA that is resistant to even harsh denaturants such as SDS, NaOH, and heat. This suicide inactivation mechanism prevents uracil excision and might play a protective role in maintaining genome integrity, as bacterial survival under hypoxic conditions is reduced due to the overexpression of MsmUDGX. Additionally, due to the importance of UDGs, the number of structures has been resolved. Moreover, high-resolution 3D structures of apo MsmUDGX, as well as uracil and DNAbound forms, are available in PDB. This review aims to provide insights into the specific structural- functional aspects of each UDG family member for theragnostic applications.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"85-96"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932476","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":"LINC01836 Promotes Colorectal Cancer Progression and Functions as ceRNA to Target SLC17A9 by Sponging miR-1226-3p.","authors":"Zhihua Xu, Yue Yu, Hao Ni, Wei Sun, Yuting Kuang","doi":"10.2174/0109298665248028231122064831","DOIUrl":"10.2174/0109298665248028231122064831","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence proves that long non-coding RNAs (lncRNAs) play a key role in the occurrence and development of colorectal cancer. However, the function and molecular mechanism of LINC01836 in CRC are still unknown.</p><p><strong>Methods: </strong>The differentially expressed lncRNAs in colorectal cancer were obtained from the RNA sequencing data. The effects of LINC01836 on colorectal cancer cells were tested in <i>in vitro</i> experiments. The mechanism of LINC01836 action was investigated through western blot, RNA immunoprecipitation assay and luciferase reporter assay. Moreover, the xenograft mouse model was conducted to examine the effects of LINC01836 <i>in vivo</i>.</p><p><strong>Results: </strong>In this study, we showed that LINC01836 was significantly elevated in colorectal cancer tissues and cells. Elevated LINC01836 expression significantly correlated with larger tumor size, positive lymph node metastasis, distant metastasis, advanced tumor-node-metastasis (TNM) stage, and poor prognosis. Furthermore, decreased expression of LINC01836 repressed proliferation, migration, and invasion <i>in vitro</i> and <i>vivo</i>, and high LINC01836 expression displayed the opposite effect. Further analysis revealed that LINC01836 could regulate the expression of SLC17A9 by competing with miR---1226-3p. Furthermore, down-regulation of LINC01836 or increased expression of miR-1226-3p markedly reversed the effects of SLC17A9 overexpression on colorectal cancer cells.</p><p><strong>Conclusion: </strong>This study showed that LINC01836 regulated the expression of SLC17A9 through sponge miR-1226-3p by acting as a competitive endogenous RNA (ceRNA), promoted the progression of colorectal cancer, and suggested a new prognostic biomarker and potential cancer treatment target for colorectal cancer.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"43-60"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138499212","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":"Feasibility of Domain Segmentation of B19V VP1u Using Intein Technology for Structural Studies.","authors":"Renuk Varayil Lakshmanan, Mavis Agbandje-McKenna, Robert McKenna","doi":"10.2174/0109298665277211231214065419","DOIUrl":"10.2174/0109298665277211231214065419","url":null,"abstract":"<p><strong>Introduction: </strong>Parvovirus B19 (B19V) is a human pathogen, and the minor capsid protein of B19V possesses a unique N terminus called VP1u that plays a crucial role in the life cycle of the virus.</p><p><strong>Objectives: </strong>The objective of this study was to develop a method for domain segmentation of B19 VP1u using intein technology, particularly its receptor binding domain (RBD) and phospholipase A2 (PLA₂) domain.</p><p><strong>Methods: </strong>RBD and PLA₂ domains of VP1u were each fused to the DnaE split inteins derived from the <i>Nostoc punctiforme</i>. Each of these precursor proteins was expressed in <i>E. coli</i>. Combining the purified precursors in equal molar ratios resulted in the formation of full-length VP1u. Furthermore, Circular Dichroism (CD) spectroscopy and PLA₂ assays were used to probe the structure and activity of the newly formed protein.</p><p><strong>Results: </strong>The CD spectrum of the full length VP1u confirmed the secondary structure of protein, while the PLA₂ assay indicated minimal disruption in enzymatic activity.</p><p><strong>Conclusion: </strong>This method would allow for the selective incorporation of NMR-active isotopes into either of the VP1u domains, which can reduce signal overlap in NMR structural determination studies.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"161-167"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513361","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":"Novel Circular RNA CircUBAP2 Drives Tumor Progression by Regulating the miR-143/TFAP2B Axis in Prostate Cancer.","authors":"Zhong Lv, Yunfeng Shi, Haoran Wu, Kai Cao, Xiaowu Liu, Chengyue Wang","doi":"10.2174/0109298665268943231103114654","DOIUrl":"10.2174/0109298665268943231103114654","url":null,"abstract":"<p><strong>Background: </strong>More and more investigations reveal that circular RNAs (circRNAs) are involved in cancer progression. CircRNA UBAP2 was closely related to prostate cancer. However, the biological function and specifical mechanism of circUBAP2 are still poorly discovered in prostate cancer (PCa).</p><p><strong>Objectives: </strong>This study aims to explore the biological function and mechanism of circUBAP2 in PCa.</p><p><strong>Methods: </strong>The levels of mRNA and proteins were assessed by qRT-PCR assay and Western blot, respectively. Cell growth, migration, and invasion ability were measured using CCK-8 assay and Transwell assay. Apoptosis was assessed using flow cytometry. The interactions between circUBAP2, miR-143, and TFAP2B were determined by luciferase report assay. The tumor growth was determined by in vivo tumor formation assay. The tumor morphology was assessed using H&E staining assay, and immunohistochemistry assay was conducted to assess the level of KI67.</p><p><strong>Results: </strong>We found circUBAP2 and TFAP2B were notably elevated, while miR-143 was largely attenuated in prostate cancer cells and tissues. CircUBAP2 was found to affect cell viability, metastasis and EMT, while attenuating the apoptosis rate of prostate cancer cells. CircUBAP2 directly targeted miR-143, and miR-143 inhibitor could reverse the effects that circUBAP2 interference-induced in prostate cancer cells. TFAP2B is directly bound to miR-143, and overexpression of TFAP2B could attenuate the influences that miR-143-induced in prostate cancer cells.</p><p><strong>Conclusion: </strong>CircUBAP2 promoted prostate cancer progression via miR-143/TFAP2B axis.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"61-73"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92156255","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":"The Features of Shared Genes among Transcriptomes Probed in Atopic Dermatitis, Psoriasis, and Inflammatory Acne: S100A9 Selection as the Target Gene.","authors":"Wei Wang, Sungbo Hwang, Daeui Park, Yong-Doo Park","doi":"10.2174/0109298665290166240426072642","DOIUrl":"10.2174/0109298665290166240426072642","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD), psoriasis (PS), and inflammatory acne (IA) are well-known as inflammatory skin diseases. Studies of the transcriptome with altered expression levels have reported a large number of dysregulated genes and gene clusters, particularly those involved in inflammatory skin diseases.</p><p><strong>Objective: </strong>To identify genes commonly shared in AD, PS, and IA that are potential therapeutic targets, we have identified consistently dysregulated genes and disease modules that overlap with AD, PS, and IA.</p><p><strong>Methods: </strong>Microarray data from AD, PS, and IA patients were downloaded from Gene Expression Omnibus (GEO), and identification of differentially expressed genes from microarrays of AD, PS, and IA was conducted. Subsequently, gene ontology and gene set enrichment analysis, detection of disease modules with known disease-associated genes, construction of the protein-protein interaction (PPI) network, and PPI sub-mapping analysis of shared genes were performed. Finally, the computational docking simulations between the selected target gene and inhibitors were conducted.</p><p><strong>Results: </strong>We identified 50 shared genes (36 up-regulated and 14 down-regulated) and disease modules for each disease. Among the shared genes, 20 common genes in PPI network were detected such as <i>LCK, DLGAP5, SELL, CEP55, CDC20, RRM2, S100A7, S100A9, MCM10, AURKA, CCNB1, CHEK1, BTC, IL1F7, AGTR1, HABP4, SERPINB13, RPS6KA4, GZMB, and TRIP13. Finally, S100A9</i> was selected as the target gene for therapeutics. Docking simulations between S100A9 and known inhibitors indicated several key binding residues, and based on this result, we suggested several cannabinoids such as WIN-55212-2, JZL184, GP1a, Nabilone, Ajulemic acid, and JWH-122 could be potential candidates for a clinical study for AD, PS, and IA <i>via</i> inhibition of S100A9-related pathway.</p><p><strong>Conclusion: </strong>Overall, our approach may become an effective strategy for discovering new disease candidate genes for inflammatory skin diseases with a reevaluation of clinical data.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"356-374"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065013","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":"Immunogenicity and Neutralization Potential of Recombinant Chimeric Protein Comprising the Catalytic Region of Gp63 of <i>Leishmania</i> and LTB against <i>Leishmania donovani</i>.","authors":"Anuja Krishnan, Gunjan Malik, Lalit C Garg","doi":"10.2174/0109298665325330240828115712","DOIUrl":"10.2174/0109298665325330240828115712","url":null,"abstract":"<p><strong>Aim: </strong>To study the inhibition potential of antibody against a recombinant chimera comprising of the catalytic epitope of gp63 of <i>Leishmania donovani</i> and B subunit of heat-labile enterotoxin (LTB) in the functional activity of L. donovani.</p><p><strong>Background: </strong>Visceral leishmaniasis, caused by the protozoan parasite <i>Leishmania donovani</i>, is a major health problem and causes mortality in tropical regions. Protozoan proteases play a crucial role in the pathogenesis of the disease and in establishing infection by countering the host's innate immune responses, namely complement-mediated lysis and phagocytosis. A surface-bound metalloprotease (gp63) has been reported to be a major virulence factor resulting in the evasion of complement- mediated lysis, cleaving host extracellular and intracellular substrates, resulting in intra- phagolysosomal survival.</p><p><strong>Methods: </strong>The epitope corresponding to the catalytic motif of gp63 of <i>Leishmania donovani</i> was fused with the B subunit of heat-labile enterotoxin, which is known to be immunogenic. The chimera was cloned to a prokaryotic expression vector and purified using Ni NTA affinity chromatography. Antibodies were generated against the purified fusion protein and analyzed for its ability to bind to the gp63 catalytic motif peptide by ELISA. The effect of fusion protein antibody on the functional activity of gp63 was evaluated by assessing the effect of purified IgGs on the protease activity and complement-mediated lysis of <i>L. donovani</i> promastigotes <i>in vitro</i>.</p><p><strong>Results: </strong>The present study reports that a recombinant chimera of the catalytic epitope of gp63 and B subunit of heat-labile enterotoxin (LTB) of <i>E. coli</i>, a potent adjuvant of humoral response can mount significant immune response towards the catalytic epitope. ELISA and Western blot analysis showed that the anti-fusion protein antiserum could recognize the native gp63. Also, it significantly inhibited the protease activity of promastigotes and subsequently increased complement-mediated lysis of the promastigotes <i>in vitro</i>.</p><p><strong>Conclusion: </strong>It could be concluded that the hybrid protein containing catalytic motif L. donovani gp63 protein and carrier protein (LTB) could elicit antibodies that could neutralise the functional activity of gp63 and thus could be a potential candidate for subunit leishmaniasis vaccine.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"696-705"},"PeriodicalIF":1.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293965","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}