FOOD CHEMISTRY
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2015
·
IF 3.391
Di Wu,Jin Yan,Peixiao Tang,Shanshan Li,Kailin Xu,Hui Li
Considering the harmful impact of food antioxidants on human bodies, thoroughly exposing their potential effects at the molecular level is important. In this study, the binding interactions of butylated hydroxyanisole (BHA), a phenolic antioxidant, and its different major metabolites tert -butylhydroquinone (TBHQ) and tert -butylbenzoquinone (TBQ) with lysozyme were examined via fluorescence, three-dimensional fluorescence, circular dichroism (CD), and ligand–protein docking studies. The three compounds caused strong quenching of lysozyme fluorescence by a static quenching mechanism but with different quenching efficiencies and different effects on the α-helix content of the lysozyme. The order of binding affinity of lysozyme for all test compounds is as follows: BHA > TBQ > TBHQ. Thermodynamic parameters indicated that hydrogen bonding and van der Waals forces perform dominant functions in the binding between these compounds and lysozyme. Furthermore, structure–affinity relationships between the model compounds and lysozyme were established on the basis of computational analyses.
研究领域:
食品科学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSICAL CHEMISTRY B
·
2021
·
IF 2.991
Minjun Ma,Xueke Gao,Zhaohui Guo,Yan Qiao
Biotin–dendrimer conjugates (such as biotin-PAMAMs-NH2) are important macromolecules in the field of host–guest chemistry and widely used systems for delivery. The similar chemical structures of the inner and outer layers of PAMAM-NH2 make it difficult to illuminate the interaction and the binding affinity of biotin-PAMAMs-NH2. By utilizing NMR techniques including 1H NMR titration, CSSF-TOCSY, STDD methods, and 2D DOSY analysis, we demonstrate a method to sort out these interactions. The methylene protons of the inner and outer layers of PAMAM-NH2 are successfully identified and accurately positioned so that the carboxylic acid groups of biotins are having ionic interactions with the outermost amine groups of PAMAM-NH2. The inner PAMAM-NH2 is protonated when reaching the isoelectric point of PAMAM-NH2, increasing the hydrodynamic radius. On the basis of the NMR experiments, a model is proposed, where the carboxylic acid groups and heterocyclic skeleton of biotin arched over the outer layers of PAMAM-NH2 like a bridge. Furthermore, using STDD epitope mapping, the binding affinity between biotin and PAMAM-NH2 was quantified. The diffusion behavior of biotin-G5 PAMAM-NH2 complex is more complicated than that of biotin-G3 PAMAM-NH2 complex due to steric hindrance. The results provide a theoretical basis for understanding these complicated drug delivery systems.
研究领域:
化学
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药物递送系统
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分子相互作用
✓ 已验证
DOI
高影响因子
STRUCTURE
·
2024
·
IF 4.4
Jian Sun,Xiangxiang Zhang,Liu Xue,Liang Cheng,Jing Zhang,Xin Chen,Zhirong Shen,Kang Li,Lai Wang,Chichi Huang,Jing Song
TIGIT is mainly expressed on T cells and is an inhibitory checkpoint receptor that binds to its ligand PVR in the tumor microenvironment. Anti-TIGIT monoclonal antibodies (mAbs) such as Ociperlimab and Tiragolumab block the TIGIT-PVR interaction and are in clinical development. However, the molecular blockade mechanism of these mAbs remains elusive. Here, we report the crystal structures of TIGIT in complex with Ociperlimab_Fab and Tiragolumab_Fab revealing that both mAbs bind TIGIT with a large steric clash with PVR. Furthermore, several critical epitopic residues are identified. Interestingly, the binding affinity of Ociperlimab toward TIGIT increases approximately 17-fold when lowering the pH from 7.4 to 6.0. Our structure shows a strong electrostatic interaction between ASP103 HCDR3 and HIS76 TIGIT explaining the pH-responsive mechanism of Ociperlimab. In contrast, Tiragolumab does not show an acidic pH-dependent binding enhancement. Our results provide valuable information that could help to improve the efficacy of therapeutic antibodies for cancer treatment.
研究领域:
免疫学
·
结构生物学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2019
·
IF 4.716
Wu Liting,Fu Shengli,Yin Xiaoxue,Guo Zheng,Wang Anli,Ye Jianmin
The recent discovery of long-lived plasma cells (LLPCs) in mammals, which provide a constant expression of specific high-affinity antibodies that mediate humoral memory, has caused a dramatic paradigm shift in the study of immunity and vaccine development. In teleost fish, there are few studies regarding the association between LLPCs and antibody production, and the affinity of the antibodies secreted by the LLPCs is poorly understood. In the present study, channel catfish (Ictalurus punctatus) were immunized with trinitrophenylated-keyhole limpet hemocyanin (TNP-KLH) to examine TNP-specific antibody titers, affinities, antibody-secreting cell (ASC) dynamic changes, and especially the affinity of secreted antibodies by LLPCs post-immunization. We demonstrated that TNP-specific LLPCs were generated starting at week 4 post-immunization, achieved a maximal number at week 8, and maintained a comparable level throughout the 18-week post-immunization period, which was correlated with the dynamics of serum antibody titers and affinity maturation in the response. The LLPCs appeared to mostly reside within, or migrate to, the anterior kidney (bone marrow-like tissue in mammals), but a small portion was also located in the spleen and peripheral blood. The antibodies produced by the LLPCs possessed high affinities, indicating that the generation and development of LLPCs were driven by affinity selection in teleosts. Collectively, the results of this study provide insights toward the evolutionary understanding of the affinity-dependent mechanism of LLPC generation and development.
研究领域:
免疫学
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兽医学
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水生生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Toxins
·
2019
·Vol. 11
·期 9
·497
·
IF 3.895
Zhi-Zhen Pan,Lian Xu,Yi-Shu Zheng,Li-Yang Niu,Bo Liu,Yan Shi,Qing-Xi Chen,Yu-Jing Zhu,Xiong Guan
Bacillus thuringiensisinsecticidal proteins (Bt toxins) have been widely used in crops for agricultural pest management and to reduce the use of chemical insecticides. Here, we have engineered Bt toxin Cry2Ab30 and bioconjugated it with 4”-O-succinyl avermectin (AVM) to synthesize Cry2Ab–AVM bioconjugate. It was found that Cry2Ab–AVM showed higher insecticidal activity againstPlutella xylostella, up to 154.4 times compared to Cry2Ab30. The binding results showed that Cry2Ab–AVM binds to the cadherin-like binding protein fragments, the 10th and 11th cadherin repeat domains in theP. xylostellacadherin (PxCR10–11), with a much higher affinity (dissociation equilibrium constantKD= 3.44 nM) than Cry2Ab30 (KD= 28.7 nM). Molecular docking suggested that the macrolide lactone group of Cry2Ab–AVM ligand docking into the PxCR10–11is a potential mechanism to enhance the binding affinity of Cry2Ab–AVM to PxCR10–11. These findings offer scope for the engineering of Bt toxins by bioconjugation for improved pest management.Keywords:Cry2Ab–AVM bioconjugate;binding affinity;molecular dockingKey Contribution:The study develops an engineered Cry2Ab by bioconjugation with 4”-O-succinyl avermectin to enhance insecticidal potency againstP. xylostella.This engineering also improves its affinity to the cadherin-like binding fragments. Homology modeling and docking study are also carried out to investigate the binding model.
研究领域:
农业生物学
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昆虫学
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蛋白质工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2016
·
IF 2.243
Evgen Multia,Heli Sirén,Karl Andersson,Jörgen Samuelsson,Patrik Forssén,Torgny Fornstedt,Katariina Öörni,Matti Jauhiainen,Marja-Liisa Riekkola
Two complementary instrumental techniques were used, and the data generated was processed with advanced numerical tools to investigate the interactions between anti-human apoB-100 monoclonal antibody (anti-apoB-100 Mab) and apoB-100 containing lipoproteins . Partial Filling Affinity Capillary Electrophoresis (PF-ACE) combined with Adsorption Energy Distribution (AED) calculations provided information on the heterogeneity of the interactions without any a priori model assumptions. The AED calculations evidenced a homogenous binding site distribution for the interactions. Quartz Crystal Microbalance (QCM) studies were used to evaluate thermodynamics and kinetics of the Low-Density Lipoprotein (LDL) and anti-apoB-100 Mab interactions. High affinity and selectivity were observed, and the emerging data sets were analysed with so called Interaction Maps. In thermodynamic studies, the interaction between LDL and anti-apoB-100 Mab was found to be predominantly enthalpy driven. Both techniques were also used to study antibody interactions with Intermediate-Density (IDL) and Very Low-Density (VLDL) Lipoproteins. By screening affinity constants for IDL-VLDL sample in a single injection we were able to distinguish affinity constants for both subpopulations using the numerical Interaction Map tool.
研究领域:
生物化学
·
分子生物学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2020
·Vol. 21
·期 24
·9529
·
IF 4.556
Shanxia Jin,Liping Liu,Mengying Fan,Yaru Jia,Ping Zhou
Pollen grain was explored as a new carrier for enzyme immobilization. After being modified with boric acid-functionalized titania, the pollen grain was able to covalently immobilize glycosylated enzymes by boronate affinity interaction under very mild experimental conditions (e.g., pH 7.0, ambient temperature and free of organic solvent). The glucose oxidase and horse radish peroxidase-immobilized pollen grain became a bienzyme system. The pollen grain also worked as an indicator of the cascade reaction by changing its color. A rapid, simple and cost-effective approach for the visual detection of glucose was then developed. When the glucose concentration exceeded 0.5 mM, the color change was observable by the naked eye. The assay of glucose in body fluid samples exhibited its great potential for practical application.Keywords:enzyme immobilization;boronate affinity;pollen grain;glucose detection
研究领域:
生物化学
·
分析化学
·
生物技术
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产品关联
DOI
PubMed
高影响因子
Food Analytical Methods
·
2022
·Vol. 15
·期 6
·1535-1544
·
IF 3.498
Li Linfang,Zhou Jinru,Wang Kuiwu,Chen Xiaojing,Fu Linglin,Wang Yanbo
Tropomyosin (TM), known as the major allergen in shellfish, has gained increasing concerns in industrialized countries, resulting in an urgent need for an accurate, simple, and sensitive method for TM detection in food products. Nucleic acid aptamers, short single-stranded oligonucleotides chains, can bind to various targets with a high affinity and specificity and hence have the potential to be used for the accurate detection of targets. Here, we proposed capillary electrophoresis-systematic evolution of ligands by exponential enrichment (CE-SELEX) for rapid selection and identification of specific aptamers against shellfish TM. A selected aptamer IX exhibited high specificity and high binding affinity against TM with K d determined (0.95 nM). In addition, the aptamer IX has great potential to be employed in the establishment of various aptasensors for TM detection in shellfish products. Furthermore, the CE-SELEX method may provide a universal and convenient method for the aptamer selection against more targets.
研究领域:
食品科学
·
分子生物学
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产品关联
DOI
高影响因子
ANALYST
·
2015
·Vol. 140
·期 13
·4648-4653
·
IF 4.107
Qian Sun,Haiyu Tian,Haoran Qu,Deheng Sun,Zhuo Chen,Liping Duan,Weibing Zhang,Junhong Qian
Two biotinylated coumarin-based fluorescent probes SPS3 and RC3 were designed for differentiating between structurally similar proteins streptavidin (SA) and avidin (AV). A substituted phenyl group is introduced onto SPS3, which may quench the fluorescence through twist intramolecular charge transfer (TICT). The fluorescence of SPS3 is turned on, by restraining the TICT process, when the fluorophore is buried at the surface of SA. RC3 is constructed by incorporating a biotin molecule to a coumarin fluorophore through a 4-atom spacer. The fluorescence intensity of RC3 is enhanced significantly when its fluorophore enters into the less polar binding pocket of AV. SPS3 and RC3 could be applied in distinguishing between SA and AV as well as in fluorescence imaging of biotin receptor over-expressed Hela cells.
研究领域:
生物化学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CONTROL
·
2022
·
IF 6.652
Feng Wang,Yuan-Yuan Yang,De-Bin Wan,Jia-Dong Li,Yi-Fan Liang,Zhen-Feng Li,Yu-Dong Shen,Zhen-Lin Xu,Jin-Yi Yang,Hong Wang,Jan Gettemans,Bruce D. Hammock,Yuan-Ming Sun
The accurate analysis of chemical isomers plays an important role in the study of their different toxic effects and targeted detection of pollutant isomers in foods . The Alternaria mycotoxins tenuazonic acid (TeA) and iso-tenuazonic acid (ITeA) are two isomer mycotoxins with the lack of single analysis methods due to the similar structures. Antibody-based immunoassays exhibit high sensitivity and superior application in isomer-specific determination. Previously, various kinds of antibodies for TeA have been prepared in our group. Herein, highly specific nanobodies (Nbs) against ITeA mycotoxin were selected from immune nanobody phage display library, and one of Nbs, namely Nb(B3G3) exhibited excellent affinity, thermal stability as well as organic solvent tolerance. By molecular simulation and docking technology, it was found that stronger interaction between Nb(B3G3) and ITeA lead to higher affinity than that for its isomer TeA. Furthermore, a sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) was established with a limit of detection (LOD) of 0.09 ng/mL for ITeA mycotoxin. The recovery rate of ITeA in spiked samples was analyzed with 84.8%–89.5% for rice, 78.3%–96.3% for flour, and 79.5%–90.7% for bread. A conventional LC-MS/MS method was used to evaluate the accuracy of this proposed icELISA, which showed a satisfactory consistent correlation. Since the convenient strategy for nanobody generation by phage display technology, this study provide new biorecognition elements and sensitive immunoassay for analysis of ITeA in foods.
研究领域:
食品安全
·
免疫学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
Biointerphases
·
2022
·Vol. 17
·期 6
·
IF 1.916
Wang Li,Cui Baocheng,Qiu Keyuan,Huang Jiao,Liang Changhai
Nitrile hydratase (NHase, EC 4.2.1.84) is an excellent biocatalyst that catalyzes the hydration of nitrile substances to their corresponding amides. Given its catalytic specificity and eco-friendliness, NHase has extensive applications in the chemical, pharmaceutical, and cosmetic industries. To improve the affinity between Rhodococcus erythropolis CCM2595-derived NHase ( Re NHase) and adiponitrile, this study used a semirational design to improve the efficiency of Re NHase in catalyzing the generation of 5-cyanopentanamide from adiponitrile. Enzyme kinetics analysis showed that Km of the mutant Re NHase B:G196Y was 3.265 mmol l −1 , which was lower than that of the wild-type NHase. The affinity of the mutant Re NHase B:G196Y to adiponitrile was increased by 36.35%, and the efficiency of the mutant Re NHase B:G196Y in catalyzing adiponitrile to 5-cyanopentamide was increased by 10.11%. The analysis of the enzyme-substrate interaction showed that the hydrogen bond length of the mutant Re NHase B:G196Y to adiponitrile was shortened by 0.59 Å, which enhanced the interaction between the mutant and adiponitrile and, thereby, increased the substrate affinity. Similarly, the structural analysis showed that the amino acid flexibility near the mutation site of Re NHase B:G196Y was increased, which enhanced the binding force between the enzyme and adiponitrile. Our work may provide a new theoretical basis for the modification of substrate affinity of NHase and increase the possibility of industrial applications of the enzyme.
研究领域:
生物化学
·
工业酶学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DENTAL MATERIALS
·
2017
·
IF 4.07
Ying Chen,Zhicen Lu,Mengke Qian,Huaiqin Zhang,Chen Chen,Haifeng Xie,Franklin R. Tay
Objectives To examine whether solvents and changing the molecular structure of 10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP) affect its chemical affinity to Yttria-stabilized tetragonal zirconia polycrystals (Y-TZP). Methods The present work investigated the chemical affinity between Y-TZP and 10-MDP dissolved in different solvents (acetone/ethanol/water or mixture) using X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and thermodynamic calculations. Shear bond strength (SBS) tests were used to evaluate the influence of different solvents on 10-MDP bonding. In addition, several phosphate ester monomer variants were created by changing the 10-MDP molecular structure. Changes included extending/shortening the spacer chain-length, and installing hydroxyl or carboxyl groups as side chains at different positions along the spacer chain. The thermodynamic parameters of the complexes formed between the 10-MDP variants and tetragonal zirconia were evaluated. Results The acquired data indicated that solvent is necessary for the formation of Zr–O–P bonds between 10-MDP and Y-TZP. Solvents affected the chemical affinity of 10-MDP to Y-TZP; acetone facilitated the best bonding, followed by ethanol. Changing the molecular structure of 10-MDP affected its chemical affinity to Y-TZP. The variants 15-MPDP, 12-MDDP, 6-hydroxyl-10-MDP and 6-carboxy-10-MDP all exhibited higher thermodynamic stability than 10-MDP when coordinated with tetragonal zirconia. In contrast, 2-MEP, 5-MPP, 10-hydroxyl-MDP, 10-carboxy-MDP, 5,6-dihydroxyl-10-MDP and 5,6-dicarboxy-10-MDP exhibited lower thermodynamic stability. Significance 10-MDP coordinates with zirconia through dissociating in solvents. Changing the molecular structure of 10-MDP theoretically affects its chemical affinity to Y-TZP.
研究领域:
牙科学
·
材料科学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）