The protein journal最新文献

{"title":"Wasp Venom: Future Breakthrough in Production of Antimicrobial Peptides.","authors":"Bikramjit Bhattacharya, Shreshtha Bhattacharya, Srinjana Khatun, Namitha A Bhaktham, M Maneesha, C Subathra Devi","doi":"10.1007/s10930-024-10242-9","DOIUrl":"https://doi.org/10.1007/s10930-024-10242-9","url":null,"abstract":"<p><p>The emergence of multi-drug-resistant pathogens and the decrease in the discovery of newer antibiotics have led to a quest for novel alternatives. Recently, wasp venom has spiked interest due to the presence of various active compounds, showcasing a diverse range of therapeutic effects. Wasps are creatures of the Hymenoptera order, and their venom chemically comprises antimicrobial peptides such as Anoplin, Mastoparan, Polybia-CP, Polydim-I, and Polybia MP1 that play a significant role in the biological effects of the venom. AMPs belong to the family of cationic peptides with α-helical structure, which exhibits a diversity of structural motifs and are crucial for innate immunity and defence in these creatures. These peptides demonstrate not only antimicrobial properties but also a wide range of other biological activities like anti-biofilm and anti-inflammatory, linked to their varying capacity to interact with biological membranes. Although wasp venom has the potential to be a cutting-edge natural source for the creation of new drugs, its usage is still restricted due to its availability and the lack of sophisticated methods for synthesizing its therapeutic components. Therefore, this review article provides insights about the therapeutic use of the wasp venom peptides against the antimicrobial-resistant pathogens, as well as its constraints and opportunities for future pharmacological development.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Acoustic Detection of α-Synuclein Fibrils.","authors":"M Brun-Cosme-Bruny, L Gerfault, V Mourier, N Torres, P Bleuet","doi":"10.1007/s10930-024-10241-w","DOIUrl":"https://doi.org/10.1007/s10930-024-10241-w","url":null,"abstract":"<p><p>Over the past decades, the incidence of Parkinson's disease (PD) cases has doubled in industrialized countries. While patients over 70 years old still represent more than half of the cases, the disease is increasingly affecting younger individuals. Environmental factors have been implicated, such as the effects of certain pesticides or chemicals on neurons, such as rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Researchers have also demonstrated the influence of genetic mutations in younger patients. A-synuclein is a protein encoded by the SNCA gene, known to undergo various mutations in hereditary cases of PD. These mutations alter the composition and spatial arrangements of α-synuclein. The proteins, originally of linear shape, aggregate during the progression of PD, forming fibrillary structures that propagate through brain tissues. Among the physical therapies investigated for treating α-synuclein aggregation, ultrasonic waves, capable of altering protein and cell behaviors, have recently been used to disrupt α-synuclein fibrils within tissues in cellular and animal models, with the hope of developing treatments based on ultrasound properties. However, detecting fibrils typically requires invasive and non-biocompatible chemical compounds or cumbersome machinery. In this study, our acoustic experimental setup allowed us to investigate the response of α-synuclein to ultrasound perturbations. By capturing the transmitted wave across proteins over a frequency range 10 kHz to 10 MHz, no ultrasound signature indicating the presence of proteins was observed.Significance Statement: The results report there is no ultrasound signature of the presence of α-synuclein fibrils, from 10 kHz to 10 MHz.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.","authors":"Kate Sheehan, Hyesoo Jeon, Sinéad C Corr, Jerrard M Hayes, K H Mok","doi":"10.1007/s10930-024-10237-6","DOIUrl":"https://doi.org/10.1007/s10930-024-10237-6","url":null,"abstract":"<p><p>Due to the large size and rapid growth of the global therapeutic antibody market, there is major interest in understanding the aggregation of protein products as it can compromise efficacy, concentration, and safety. Various production and storage conditions have been identified as capable of inducing aggregation of polyclonal and monoclonal antibody (mAb) therapies such as low pH, freezing, light exposure, lyophilisation and increased ionic strength. The addition of stabilising excipients to these therapeutics helps to combat the formation of aggregates with future aggregation inhibition mechanisms involving the introduction of point mutations and glycoengineering within aggregation prone regions (APRs). Antibody aggregation also plays an integral role in the pathogenesis of a condition known as amyloid light chain (AL) amyloidosis which is characterised by the production of improperly folded and amyloidogenic immunoglobulin light chains (LCs). Current diagnostic tools rely heavily on histological staining with their future moving towards amyloid component identification and proteomic analysis. For many years, treatment options designed for multiple myeloma (MM) have been applied to AL amyloidosis patients by depleting plasma cell numbers. More recently, treatment strategies more specific to this condition have been developed with many designed to recognize amyloid fibrils and trigger their degradation without causing systemic plasma cell cytotoxicity. Amyloid fibrils in AL disease and aggregates in antibody therapeutics are both formed through the oligomerisation of misfolded / modified proteins attempting to reach a thermodynamically stable, free energy minimum that is lower than the respective monomers themselves. Although the final morphologies are different, by understanding the principles underlying such aggregation, we expect to find common insights that may contribute to the development of new and effective methods of antibody aggregation and/or amyloidosis management. We envision that this area of research will continue to be very relevant in both industry and clinical settings.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DAAO Mutant Sites among Different Mice Strains and Their Effects on Enzyme Activity.","authors":"Zhou Yu-Cong, Fu Sheng-Ling, Liu Hao","doi":"10.1007/s10930-024-10235-8","DOIUrl":"https://doi.org/10.1007/s10930-024-10235-8","url":null,"abstract":"<p><p>Previous studies reported that _D-amino acid oxidase (DAAO) activity was closely associated with neuropathic pain, cognitive characteristics of schizophrenia and so on. To determine DAAO mutant sites in different strains of mice and their effects on enzyme activity, we successfully constructed a prokaryotic expression system for heterologous expression of DAAO in vitro. There were total five nucleotide mutations distributed in exons 2, 8, 9, 10 of C57 mice. Three mutations located on exons 8 and 9 were synonymous mutations and had no variation on the encoded amino acid. The remaining two mutations in exons 2 (V64A) and 10 (R295H) were non-synonymous mutations, which might affect enzymatic activity and protein structure of mDAAO. Based on the determination of the kinetic constants and IC₅₀ of mDAAO mutants in vitro, the differences in amino acid levels at these two sites (V64A, R295H) increased the affinity of C57 DAAO with substrate and enhanced its catalytic efficiency. Besides, the IC₅₀ value of C57 DAAO was less than that of Balb/c and other DAAO mutants (SUN: reducted by about 11.9%; CBIO: reducted by about 26.5%), which meant that the affinity of C57 DAAO with CBIO was higher.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Recombinant Stonustoxin Alpha Subunit and Preparation of polyclonal antiserum for Stonustoxin Neutralization Studies.","authors":"Amir Sajjad Hojjati-Razgi, Shahram Nazarian, Hossein Samiei-Abianeh, Amir Vazirizadeh, Emad Kordbacheh, Seyed Mojtaba Aghaie","doi":"10.1007/s10930-024-10203-2","DOIUrl":"10.1007/s10930-024-10203-2","url":null,"abstract":"<p><p>Stonustoxin (SNTX) is a lethal protein found in stonefish venom, responsible for many of the symptoms associated with stonefish envenomation. To counter stonefish venom challenges, antivenom is a well-established and effective solution. In this study, we aimed to produce the recombinant alpha subunit protein of Stonustoxin from Synanceia horrida and prepare antibodies against it The SNTXα gene sequence was optimized for E. coli BL21 (DE3) expression and cloned into the pET17b vector. Following purification, the recombinant protein was subcutaneously injected into rabbits, and antibodies were extracted from rabbit´s serum using a G protein column As a result of codon optimization, the codon adaptation index for the SNTXα cassette increased to 0.94. SDS-PAGE analysis validated the expression of SNTXα, with a band observed at 73.5 kDa with a yield of 60 mg/l. ELISA results demonstrated rabbits antibody titers were detectable up to a 1:256,000 dilution. The isolated antibody from rabbit´s serum exhibited a concentration of 1.5 mg/ml, and its sensitivity allowed the detection of a minimum protein concentration of 9.7 ng. In the neutralization assay the purified antibody against SNTXα protected mice challenged with 2 LD50. In conclusion, our study successfully expressed the alpha subunit of Stonustoxin in a prokaryotic host, enabling the production of antibodies for potential use in developing stonefish antivenom.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":"627-638"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}