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LWT-FOOD SCIENCE AND TECHNOLOGY · 2025 · IF 6.6

Effects of non-thermal treatments on goat whey protein allergenicity: A study based on conformational and linear epitopes

Zhi Cao,Zhengshi Chang,Yumei Gao,Bingjie Xue,Yanhui Yang,Lili Zhao,Wupeng Ge

This study focused on the effects of various non-thermal treatments on the antigenicity of goat milk whey protein (GWP), and the mechanism of reducing antigenicity was also discussed from the perspective of conformation epitope and linear epitope. The optimal reduction rate of antigenicity was 38.83% for β-Lg and 29.27% for α-La after 600MPa/30 min of ultra-high pressure (UHP) treatment. Non-thermal treatments not only changed the structure of GWP, but also increased or decreased the number, exposure degree and antigen binding rate of antigenicity peptides. Three kinds of non-thermal treatments reduced the GWP antigenicity by different mechanisms. UHP and PEF treatments reduced antigenicity mainly through altering conformational epitopes, while CP treatment reduced antigenicity by both altering conformational epitopes and decreasing antigenicity peptides. This result provided new ideas and technologies to reduce milk protein antigenicity.

CAS / MDL: 75-05-8 64-18-6
研究领域: 食品科学 · 免疫学 · 蛋白质组学
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FOOD CHEMISTRY · 2023 · IF 8.8

The decrease of Ara h 2 allergenicity by glycation is determined by reducing sugar chain length and isomers

Ping Yang,Xumei Wang,Hui Wang,Yueming Hu,Pingwei Wen,Zongcai Tu

The mechanism of the effect of reducing sugar chain length and isomers on the allergenicity of Ara h 2 after glycation was investigated. Ara h 2 was more prone to glycation with ribose which had a short chain length. The glycation sites of Ara h 2 after glycation with galactose were higher than the glycation sites in galactose’s isomers-Ara h 2 conjugates, which might be affected by the configuration differences at position C-4 and the small steric effects in terminal groups –CHO of galactose. Ara h 2-ribose conjugate had the lowest allergenicity, and glycation with galactose was more capable of reducing Ara h 2 allergenicity than its isomers. The results indicated that glycation with ribose caused conformational epitope destruction and linear epitope masking of Ara h 2 greatly. Furthermore, since the small steric effects of –CHO, galactose was more capable of reducing Ara h 2 allergenicity than fructose. This study will provide a theoretical basis for selecting appropriate reducing sugars and preparing hypoallergenic products containing peanuts.

CAS / MDL: 643-79-8
研究领域: 食品科学 · 过敏学 · 生物化学
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Journal of Pharmaceutical Analysis · 2024 · IF 6.1

Comparative study of trastuzumab modification analysis using mono/multi-epitope affinity technology with LC-QTOF-MS

Chengyi Zuo,Jingwei Zhou,Sumin Bian,Qing Zhang,Yutian Lei,Yuan Shen,Zhiwei Chen,Peijun Ye,Leying Shi,Mao Mu,Jia-Huan Qu,Zhengjin Jiang,Qiqin Wang

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the MOF@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and LC-QTOF-MS. Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked PB model, faster modification trends were monitored in the spiked serum and patients’ sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients’ sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

研究领域: 药学 · 分析化学 · 生物技术 · 生物化学
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FOOD CHEMISTRY · 2024 · IF 8.5

Optimizing β-Lactoglobulin antigenicity through single enzyme hydrolysis: Exploring structural changes and effects on linear epitopes

Peng Sun,Xiaomeng Wu,Qi Sun,Qing Zhao,Guangqing Mu,Fanhua Kong

β-lactoglobulin (β-LG) is the major allergen in dairy products, but research on the optimal conditions for antigen reduction in β-LG using different enzymes remains limited. Therefore, this study aims to investigate the antigenicity, structural characteristics, and peptide distribution of advantageous protease hydrolysates capable of eliminating the allergenic epitopes of β-LG selected via bioinformatics tools. The results showed that under optimal enzymatic hydrolysis conditions, the antigen reduction rates for the four advantageous proteases acting on β-LG were 47.37 % (pepsin), 33.54 % (chymotrypsin A), 38.71 % (papain), and 45.91 % (stem bromelain), respectively. The four proteases effectively degraded β-LG, causing shorter peptide chain formation, reduced content of highly ordered α-helix, decreased fluorescence intensity, and lower surface hydrophobicity. Furthermore, they cleaved the linear epitopes of β-LG into peptides of varying sizes, leading to different antigen reduction rates among the hydrolysates. These findings provide a theoretical basis for developing targeted enzymatic hydrolysis technologies and low-allergenicity dairy-based materials.

CAS / MDL: 643-79-8 9045-23-2
研究领域: 食品科学 · 过敏学 · 生物化学
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FOOD CHEMISTRY · 2025 · IF 9.8

Investigation of conformational and epitope alterations of shrimp tropomyosin under α-dicarbonyl glycation and conformation-allergenicity relationship

Lichun Liu,Ziye Zhang,Zihao Li,Hao Wang,Zhenxing Li,Hong Lin

The incidence of shrimp-induced food allergy is increasing yearly. Glycation has been reported to reduce shrimp tropomyosin (TM) allergenicity, and how advanced glycation end products (AGEs) impact TM allergenicity has garnered worldwide attention. This work investigated the conformational and epitope alterations of TM under α-dicarbonyl compounds (glyoxal (GO), methylglyoxal (MGO), butanedione (BU)) glycation and conformation-allergenicity relationship. As the results, α-dicarbonyl compounds glycation induced high glycation and TM conformational alterations. AGEs glycation sites on TM epitopes were identified by HPLC-MS/MS, with epitope destruction rates of 62.5 %, 50 % and 62.5 % for GO-TM, MGO-TM and BU-TM, respectively. Immunological results revealed TM glycated by α-dicarbonyls compounds performed weaker IgE binding by 33.38–33.86 %, while GO and MGO reduced IgG binding by 63.60 % and 77.72 %, respectively, suggesting α-dicarbonyls compounds reduced TM allergenicity via AGEs-induced epitope loss and conformational changes. This investigation could provide novel insights into how α-dicarbonyls compounds reduce TM allergenicity and prevent shrimp-induced allergy.

CAS / MDL: 7558-80-7
研究领域: 免疫学 · 食品科学 · 生物化学
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MOLECULAR IMMUNOLOGY · 2018 · IF 3.188

A novel Aβ epitope vaccine based on bacterium-like particle against Alzheimer’s disease

Lu Fu,Yongqing Guo,Yao Sun,Yue Dong,Jiaxin Wu,Bin Yu,Haihong Zhang,Xianghui Yu,Hui Wu,Wei Kong

Amyloid-beta (Aβ) plaque accumulation in the brain is one of the hallmarks of Alzheimer’s disease (AD). Immunotherapy against Aβ was considered a potential strategy for reducing the Aβ load in the brain. However, none of the Aβ immunotherapies have produced clinically meaningful results to date, due to poor safety or lack of efficacy. Thus, we aimed to design a safe and effective vaccine against AD. In this study, we used bacterium-like particles (BLPs) as carriers and different copy numbers of the Aβ 1-6 peptide as epitopes to design four Aβ active immunization vaccines. The epitopes containing different copy numbers of the Aβ 1-6 peptide were specifically loaded on the surface of BLPs via fusion with a peptidoglycan anchoring domain. These four BLP-based Aβ vaccines successfully induced high levels of Aβ42-specific antibodies in mice. However, none of the vaccines induced a T-cell-mediated immune response. Importantly, the antibodies induced by these four vaccines were effective in blocking Aβ42 oligomer toxicity at the cellular level. Among the four vaccines, 6copy-Aβ 1-6 -PA-BLP was the most effective in inducing Aβ-specific antibodies, indicating that a suitable epitope copy number is critical for high immunogenicity of the BLP-based vaccine. Furthermore, high levels of serum Aβ-specific antibodies could still be detected 3 months after the final administration of 6copy-Aβ 1-6 -PA-BLP. Thus, 6copy-Aβ 1-6 -PA-BLP may be a potential therapeutic treatment for AD.

CAS / MDL: 920-66-1
研究领域: 生物医学 · 神经科学 · 疫苗开发
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CHEMICAL PAPERS · 2022 ·Vol. 76 ·期 6 ·3937-3947 · IF 2.146

N-terminal epitope surface imprinted particles for high selective cytochrome c recognition prepared by reversible addition- fragmentation chain transfer strategy

Li Xinxin,Lin Min,Zhang Hongfeng,Ji Wenquan,Shi Yuhan,Qi Zhiyang,Fu Tianwen,Li Qinran,Deng Qiliang

A kind of surface imprinted particles was synthesized to recognize cytochrome c (Cyt c) by a novel strategy combining reversible addition-fragmentation chain transfer (RAFT) radical polymerization and epitope surface imprinting. N-terminal epitope nonapeptide of Cyt c was chosen as the template. The selectivity of these particles for protein recognition was obviously improved due to the selection of epitopes rather than the whole protein as templates and the controllable length of polymer shell chain. After epitope had been modified on the surface of silica, the surface imprinted polymer with controlled imprinted layer was synthesized with monomers and cross-linkers by RAFT radical polymerization strategy. The epitope surface imprinted particles were obtained after the peptide removed and trithioester group destruction by hexylamine. The binding capacity of N-terminal peptide reached 1.88 mg peptide per gram with imprinting factor (IF) as 2.42 while the binding capacity of Cyt c reached 8.89 mg protein per gram with IF as 1.71, which were obviously higher than the IF of the material without RAFT strategy. Moreover, Cyt c could be selectively recognized by the epitope surface imprinted particles even in presence of the competitive proteins with different molecular weight and isoelectric point. The performance of protein recognition remained 90% after five cycles of adsorption and desorption. All these results demonstrated that the epitope surface imprinted particles prepared by RAFT strategy are promising to achieve the protein recognition with higher recognition ability, selectivity and reusability.

研究领域: 生物化学 · 分子生物学
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BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS · 2013 · IF 3.848

Anti-HIV-1 activity and structure–activity-relationship study of a fucosylated glycosaminoglycan from an echinoderm by targeting the conserved CD4 induced epitope

Wu Lian,Mingyi Wu,Ning Huang,Na Gao,Chuang Xiao,Zi Li,Zhigang Zhang,Yongtang Zheng,Wenlie Peng,Jinhua Zhao

Background Fucosylated glycosaminoglycan (FG) is a novel glycosaminoglycan with a chondroitin sulfate-like backbone and fucose sulfate branches. The aim of this study is to investigate the mechanism and structure–activity relationships (SAR) of FG for combating HIV-1 infection. Methods Anti-HIV activities of FGs were assessed by a cytopathic effect assay and an HIV-1 p24 detection assay. The biomolecule interactions were explored via biolayer interferometry technology. The SAR was established by comparing its anti-HIV-1 activities, conserved CD4 induced (CD4i) epitope-dependent interactions and anticoagulant activities. Results FG efficiently and selectively inhibited the X4- and R5X4-tropic HIV-1 infections in C8166 cells with little cytotoxicity against C8166 cells and PBMCs. Our data indicated that FG bound to gp120 with nanomolar affinity and may interact with CD4i of gp120. Additionally, the CD4i binding affinity of FG was higher than that of dextran sulfate. SAR studies suggested that the unique sulfated fucose branches account for the anti-HIV-1 activity. The molecular size and present carboxyl groups of FG may also play important roles in various activities. Notably, several FG derivatives showed higher anti-HIV-1 activities and much lower anticoagulant activities than those of heparin. Conclusions FG exhibits strong activity against X4- and R5X4-tropic HIV-1 infections. The mechanism may be related to targeting CD4i of gp120, which results in inhibition of HIV-1 entry. The carboxyl group substituted derivatives of FG (8.5–12.8   kDa), might display high anti-HIV-1 activity and low anticoagulant activity. General significance Our data supports further the investigation of FG derivatives as novel HIV-1 entry inhibitors targeting CD4i.

CAS / MDL: 25952-53-8
研究领域: 病毒学 · 药理学 · 分子生物学
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FOOD CHEMISTRY · 2021 · IF 7.514

Two binding epitopes modulating specificity of immunoassay for β-agonist detection: Quantitative structure–activity relationship

Lanteng Wang,Jin Wang,Ang Zhang,Xin-an Huang,Hongtao Lei

A growing number of β -agonists are illegally using for reducing animal fat deposition in animals, but the development of analytical methods always lags behind the emergence of new illegal compounds. Therefore, class specificity antibody-based immunoassays that can detect a great many β -agonists are important for timely supervision. In this study, a competitive inhibition enzyme-linked immunosorbent assay (ciELISA) based on a clenbuterol monoclonal antibody was developed to recognize 23 β -agonists and analogues. Holographic and three-dimensional quantitative structure–activity relationship (HQSAR and 3D QSAR) revealed that there are two critical binding epitopes on β -agonist hapten affecting antibody specificity, and these epitopes have been further validated using a ractopamine antibody with narrow specificity. Tert -butyl at C-2′ epitope is needed to generate class specific antibodies, and different characteristics of substituents at benzene ring epitope would adjust antibody specificity. This investigation could provide reference for future design of β -agonist haptens.

研究领域: 食品安全 · 免疫学 · 药物化学
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ACS Omega · 2023 · IF 4.1

Enhancing Cytochrome C Recognition and Adsorption through Epitope-Imprinted Mesoporous Silica with a Tailored Pore Size

Dandan Cheng,Xin Han,Jiawen Zou,Zhenyu Li,Meiru Wang,Yuqing Liu,Kexuan Wang,Yan Li

We have reported the synthesis of epitope-imprinted mesoporous silica (EIMS) with an average pore size of 6.2 nm, which is similar to the geometrical size of the target protein, cytochrome C (Cyt c, 2.6 × 3.2 × 3.3 nm3), showing great recognition and large-scale adsorption performance. The characteristic fragment of Cyt c was used as a template and docked onto the surface of C16MIMCl micelles via multiple interactions. Nitrogen adsorption–desorption and transmission electron microscopy confirmed the successful preparation of EIMS. Due to the ordered pore structure, larger pore size, and high specific surface area, the prepared EIMS show superior specificity (IF = 3.8), excellent selectivity toward Cyt c, high adsorption capacity (249.6 mg g–1), and fast adsorption equilibrium (10 min). This study demonstrates the potential application of EIMS with a controllable pore size for high-effective and large-scale separation of Cyt c, providing a new approach for effective biomacromolecular recognition.

研究领域: 生物化学 · 材料科学 · 蛋白质工程
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Food Bioscience · 2024 · IF 4.8

Modification of structure, epitope and allergenicity on heat-stressed ovalbumin by resveratrol

Caiying Yang,Ying Zhang,Xiaoya Zhou,Zhihua Wu,Jinyan Gao,Hongbing Chen,Ping Tong

Allergen modification is a novel strategy for preventing and treating food allergy. Resveratrol (RES) can be used as a modifying ligand for allergens, but the interaction mechanism between RES and allergens is still not detailed, and the ramifications of this interaction on the structure, epitope and allergenicity of allergens are also lacking a clear explanation. In addition, the application of heat can promote protein structure to unfold and expose more binding sites to facilitate interaction. Therefore, in this study, ovalbumin (OVA) was selected as the allergen model and was heated to expose more binding sites. The effects of the interaction between RES and heat-stressed ovalbumin (HOVA) on allergen structure, epitope and allergenicity were investigated by combining routine experimental analysis and computer simulation. Results showed heat stress at 323 K for 15 min could better unfold the molecular structure of OVA. On this basis, the interaction between RES and OVA was strengthened, which showed a static quenching of the ground state complex with binding affinity of 1.25 × 10 6  L/mol. The binding of RES induced the variation of protein microenvironment, and the overall structure tended to disordered direction. Computer simulation had shown RES could directly act on the IgE epitope region (AA251-260) of the OVA. The allergenicity evaluation experiment further indicated the combination of RES alleviated the IgE binding capacity of HOVA. These findings are helpful to further study the mechanism of RES ligand modification to change food allergy.

CAS / MDL: 10102-40-6
研究领域: 食品科学 · 过敏反应 · 生物化学 · 分子生物学
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FOOD CHEMISTRY · 2020 · IF 6.306

Mechanism of the effect of 2, 2′-azobis (2-amidinopropane) dihydrochloride simulated lipid oxidation on the IgG/IgE binding ability of ovalbumin

Jing-jing Zhang,Zong-cai Tu,Hui Wang,Yue-ming Hu,Peng-cheng Du,Yi-peng Yang

In this work, the mechanism of the effect of lipid oxidation on the IgG/IgE binding ability of ovalbumin (OVA) was investigated via the peroxyl radicals produced by 2, 2′-azobis (2-amidinopropane) dihydrochloride to simulate lipid oxidation. Results showed that the structure of OVA unfolded partially with an increase in oxidation degree, leading to the exposure of the allergenic epitopes and increasing the IgG/IgE binding ability of OVA. Nine oxidation sites were found on the α-helix, and these sites may unwind the α-helix and expose the allergenic epitopes on the OVA surface, leading to antibody recognition and combination. Consequently, the IgG/IgE binding ability of OVA was increased. In conclusion, the allergenic capacity of OVA can be promoted by modifying peroxyl radical oxidation in processing egg products.

CAS / MDL: 2997-92-4
研究领域: 食品科学 · 免疫学
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