JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-11
·
IF 9.429
Hsieh Yuan-Chin,Liao Jun-min,Chuang Kuo-Hsiang,Ho Kai-Wen,Hong Shih-Ting,Liu Hui-Ju,Huang Bo-Cheng,Chen I-Ju,Liu Yen-Ling,Wang Jaw-Yuan,Tsai Hsiang-Lin,Su Yu-Cheng,Wang Yen-Tseng,Cheng Tian-Lu
Background Humanization of mouse monoclonal antibodies (mAbs) is crucial for reducing their immunogenicity in humans. However, humanized mAbs often lose their binding affinities. Therefore, an in silico humanization method that can prevent the loss of the binding affinity of mAbs is needed.Methods We developed an in silico V(D)J recombination platform in which we used V(D)J human germline gene sequences to design five humanized candidates of anti-tumor necrosis factor (TNF)-α mAbs (C1–C5) by using different human germline templates. The candidates were subjected to molecular dynamics simulation. In addition, the structural similarities of their complementarity-determining regions (CDRs) to those of original mouse mAbs were estimated to derive the weighted interatomic root mean squared deviation (wRMSDi) value. Subsequently, the correlation of the derived wRMSDi value with the half maximal effective concentration (EC50) and the binding affinity (KD) of the humanized anti-TNF-α candidates was examined. To confirm whether our in silico estimation method can be used for other humanized mAbs, we tested our method using the anti-epidermal growth factor receptor (EGFR) a4.6.1, anti-glypican-3 (GPC3) YP9.1 and anti-α4β1 integrin HP1/2L mAbs.Results The R2 value for the correlation between the wRMSDi and log(EC50) of the recombinant Remicade and those of the humanized anti-TNF-α candidates was 0.901, and the R2 value for the correlation between wRMSDi and log(KD) was 0.9921. The results indicated that our in silico V(D)J recombination platform could predict the binding affinity of humanized candidates and successfully identify the high-affinity humanized anti-TNF-α antibody (Ab) C1 with a binding affinity similar to that of the parental chimeric mAb (5.13 × 10−10). For the anti-EGFR a4.6.1, anti-GPC3 YP9.1, and anti-α4β1 integrin HP1/2L mAbs, the wRMSDi and log(EC50) exhibited strong correlations (R2 = 0.9908, 0.9999, and 0.8907, respectively).Conclusion sOur in silico V(D)J recombination platform can facilitate the development of humanized mAbs with low immunogenicity and high binding affinities. This platform can directly transform numerous mAbs with therapeutic potential to humanized or even human therapeutic Abs for clinical use.Graphical Abstract
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高影响因子
PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY
·
2021
·
IF 2.162
Shu Ye,Fan Zhang,Ying Xu,Yun Sun,Benwei Zhu,Fang Ni,Zhi Zhou,Zhong Yao
In this study, a series of acidic or alkaline polypeptide chains were designed and grafted onto DEG-AM resin using Fmoc solid-phase synthesis to study the relationship between enzyme conformation and carrier surface charge. β-d-glucosidase (βGase) was then immobilized onto these modified carriers by adsorption. Each form of immobilized βGase showed decreasing specific activity compared to that of the free. It could be attributed to both the changes in the enzyme conformation and the decrease in mass transfer efficiency. The optimum temperature of free βGase, DEG@B3-βGase is 55 °C, which of DEG@A3-βGase is 65 °C and they all have the highest activity at pH 5. The Ea values of free βGase, DEG@A3-βGase, and DEG@B3-βGase are 0.546 kJ/mol, 0.224 kJ/mol, and 0.446 kJ/mol, and the Km values were 1.30 mmol/L, 1.44 mmol/L and 2.63 mmol/L, respectively. It shows that free βGase and DEG@A3-βGase are more similar. Meanwhile, the free βGase (1.0 g/L, pH 5.0) stored at 4 °C has a shorter half-life (t1/2), which is only 9 days. However, the half-life of DEG@B3-βGase and DEG@A3-βGase is 20 days and over 60 days, indicating that the negative charged surface was conducive to maintenance of the structure and catalytic property of βGase.
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Materials Today Physics
·
2021
·
IF 9.298
Chengyuan Tang,Xinyu Shen,Siyao Yu,Yuan Zhong,Zhenyu Wang,Junhua Hu,Min Lu,Zhennan Wu,Yu Zhang,William W. Yu,Xue Bai
Inorganic CsPbX 3 (X = Cl, Br, I) perovskite nanocrystals (PNCs) have a great promise for LED applications due to their high brightness and tunable emission. However, the long chain capping ligands such as oleylamine and oleic acid function are electrically insulating layers to hinder the charge carrier injection and transport, limiting the device performances. To overcome the limitations, p -iodo-D-phenylalanine (PIDP) was used in the post-treatment process of PNCs to partially substitute the long insulating ligands to improve the conductivity of CsPbI 3 PNC films. Besides, the surface defects were also passivated by PIDP, increasing the radiative decay rate and decreasing the non-radiative decay rate, thus enhanced the photoluminescence quantum yield of the PNCs. As a result, highly efficient PNC LEDs were obtained with an external quantum efficiency of 12.4% and a peak luminance of 2000 cd m −2 .
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JOURNAL OF APPLIED POLYMER SCIENCE
·
2021
·Vol. 138
·期 36
·50926
·
IF 3.125
Haoran Xu,Yanjun Hou,Rui Li,Lijing Chang,Yang Ma,Shoulei Miao,Haijun Niu
Two donor units (D)-acceptor units (A) type monomers were synthesized by Stille coupling reaction, and then three D-A type hybrid polymers based on 3,4-ethylenedioxythiophene and various benzodiazoles were synthesized by electrochemical polymerization. Spectroelectrochemical and kinetic studies of these polymers showed that all polymer films exhibited excellent electrochromic behavior, obvious optical contrast, and excellent stability. Among them, the response time of P3 film was the shortest ( t c = 1.6 s, t b = 2.2 s), the coloring efficiency of P2 film was the highest ( CE = 333 cm 2 ·C −1 ), and the stability of P1 was the best (the ΔT loss of P1 after 1000 s cycles is only 2.3%). Therefore, these data prove that these new polymers have great potential in applications as electrochromic materials.
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Bioresources and Bioprocessing
·
2021
·Vol. 8
·期 1
·1-15
·
IF 4.578
Tan Xu,Zhang Sheng,Song Wei,Liu Jia,Gao Cong,Chen Xiulai,Liu Liming,Wu Jing
In this study, a four-enzyme cascade pathway was developed and reconstructed in vivo for the production of d - p -hydroxyphenylglycine (D-HPG), a valuable intermediate used to produce β-lactam antibiotics and in fine-chemical synthesis, from l -tyrosine. In this pathway, catalytic conversion of the intermediate 4-hydroxyphenylglyoxalate by meso -diaminopimelate dehydrogenase from Corynebacterium glutamicum ( Cg DAPDH) was identified as the rate-limiting step, followed by application of a mechanism-guided “conformation rotation” strategy to decrease the hydride-transfer distance d (C6HDAP−C4NNADP) and increase Cg DAPDH activity. Introduction of the best variant generated by protein engineering ( Cg DAPDH BC621/D120S/W144S/I169P with 5.32 ± 0.85 U·mg −1 specific activity) into the designed pathway resulted in a D-HPG titer of 42.69 g/L from 50-g/L l -tyrosine in 24 h, with 92.5% conversion, 71.5% isolated yield, and > 99% enantiomeric excess in a 3-L fermenter. This four-enzyme cascade provides an efficient enzymatic approach for the industrial production of D-HPG from cheap amino acids.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Pengfei Liu,Jiaojiao Zhang,Yan Qiao,Xianglin Hou,Yu Liu,Yingxiong Wang
Using environment-friendly catalysts to convert biomass into compounds with high values is one of the central topics of green chemistry. In this work, [Ch][Pro] (cholinium as the cation and l-proline as the anion) ionic liquid was synthesized and applied as a model catalyst in the production of deoxyfructosazine (DOF) and fructosazine (FZ) from d-glucosamine (GlcNH2). The 13C NMR chemical shift titration experiments and the diffusion-ordered NMR spectroscopy (DOSY) measurements showed that, when the [Ch][Pro] interacted with GlcNH2, the l-proline anion ([Pro]−) played a major catalytic role instead of cholinium cation ([Ch]+). The effects of the reaction temperature and the amount of [Ch][Pro] on the product yields were surveyed. The experimental results showed that the highest DOF yield (33.78%) was obtained after 30 min at 100 °C when the molar ratio of [Ch][Pro]/GlcNH2 was 1. Moreover, in situ1H NMR and in situ13C NMR experiments were applied to monitor the reaction process with [Ch][Pro] as the catalyst. The reactive intermediate, dihydrofructosazine, was clearly detected by these in situ techniques. Accordingly, a possible reaction pathway was proposed. By applying other amino acids as the anions, we also prepared five other [Ch][AA] ionic liquids, and they showed different catalytic activities and selectivity in the GlcNH2 self-condensation reaction.
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THERMOCHIMICA ACTA
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2020
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IF 2.762
Jiacheng Ji,Sum-Wai Chiang,Mengjing Liu,Xin Liang,Jia Li,Lin Gan,Yanbing He,Baohua Li,Feiyu Kang,Hongda Du
In this work, we report a fabrication of oriented carbon fibres/alumina/silicon rubber composites by 3-D printing. The 3-D printed composites possess higher thermal conductivity up to 7.36 W/m K at 12 vol% CFs and 30 vol% alumina loading than that of cast composites (4.22 W/m K) at the same components. The orientation caused by 3-D printing produces a synergism of the thermal conductivity enhancement for CFs and alumina hybrid filled composites. We attribute the synergism to the decrease of thermal interface resistance, while the reduction of thermal interface resistance has a bigger effect on thermal conductivity of CASR composites. This study provides a novel way to obtain thermal conductive composites with orientation, which has a great significance for the development of high-performance thermal conductive products.
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MICROCHEMICAL JOURNAL
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2023
·
IF 4.8
Ying-ying Hu,Xiao-qin Wu,He-ping Shi,Xue-hong Wei
The nature of amino acids as the building blocks of proteins leading to detection and identification is a current hot topic. Therefore, {[Zn 3 (L − ) 2 (HBTC 2− ) 2 ]·2H 2 O·CH 3 CN} n ( Zn-1 , H 3 BTC = 1,3,5-benzenetricarboxylic acid, HL = 6-aminonicotinic acid, CH 3 CN = acetonitrile), a 2D Zn-MOF which can sensitively detect and selectively recognize D -tyrosine was synthesized by solvothermal method . Identification of D -tyrosine was determined by increasing fluorescence intensity and red-shifting of the emission wavelength . Zn-1 is highly stable in methanol (MeOH) and aqueous solution (H 2 O), so it was dissolved in them as fluorescence probes, namely Zn-1/MeOH probe and Zn-1/H 2 O probe , respectively. The two probes worked for lower limits of detection, 8.93 × 10 −2 μM for Zn-1/MeOH probe and 79.70 × 10 −2 μM for Zn-1/H 2 O probe . The Stern-Volmer quenching constant of Zn-1/MeOH probe is 1.28 × 10 4 M −1 and of Zn-1/H 2 O probe is 4.55 × 10 2 M −1 . In addition, the two probes still show excellent immunity to interference under the interference of 18 amino acids. Zn-1/H 2 O probe was also applied to the determination of D -tyrosine in real milk samples with good results. This study provides a fast, simple, convenient and relatively accurate method for detecting D -tyrosine.
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PHARMACEUTICAL BIOLOGY
·
2018
·
IF 1.918
Wenlong Yang,Guanlin Zhou,Shubing Zou,Wentao Yang,Aihong Liu,Shuilin Sun,Baogang Xie
Context: d-Glucaro-1,4-lactone (1,4-GL) exists in many vegetables and fruits. Metabonomics has not been used to investigate the role of 1,4-GL in preventing liver cancer.Objective: The pharmacological effects and metabolite alterations of 1,4-GL on the prevention of diethylnitrosamine (DEN)-induced liver cancer were investigated.Materials and methods: Ten healthy Sprague–Dawley rats served as control and 46 were used to establish rat liver cancer model. 1HNMR-based metabonomics was used to compare the effects of oral 1,4-GL (50 mg/kg) in liver cancer rats (n = 26) after 10 consecutive weeks of intervention. The amino acids in rat serum were quantified by HPLC-UV, and the changes in Fischer’s ratio were calculated.Results: The 20-week survival rate of DEN-induced liver cancer rats administered with oral 1,4-GL was increased from 45.0 to 70.0% with reduced carcinogenesis of the liver and significantly lowered serum α-fetoprotein level (14.28 ± 2.89 ng/mL vs. 18.56 ± 4.65 ng/mL, p = 0.012). The serum levels of leucine, valine, 3-hydroxybutyrate, lactate, acetate and glutamine in the DEN + 1,4-GL group returned to normal levels compared with those of the DEN group on week 20. Fischer’s ratio in the rat serum of DEN group was 1.62 ± 0.21, which was significantly lower than that in healthy rats (2.3 ± 0.12). However, Fischer’s ratio increased to 1.89 ± 0.22 in the DEN + 1,4-GL group.Discussion and conclusions: 1,4-GL exerted positive effects on liver carcinogenesis in rats by pathological examination and metabonomic analysis. Its mechanism may be related to the restoration of amino acid and energy metabolism.
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JOURNAL OF MOLECULAR LIQUIDS
·
2018
·
IF 4.513
Kemeng Shi,Christian Marcus Pedersen,Zhaohui Guo,Yanqiu Li,Hongyan Zheng,Yan Qiao,Tuoping Hu,Yingxiong Wang
The tautomer distributions of d ‑fructose, a popular model compound for biorefinery , in various lower alcohols and DMSO‑ d 6 (ROHs/DMSO‑ d 6 ) mixtures at 298 K were investigated by quantitative 13 C NMR. The tautomer distributions of d ‑fructose in ethanol/DMSO‑ d 6 and methanol/DMSO‑ d 6 with different volume ratios of alcohols to DMSO‑ d 6 were also examined. For these normal alcohols (methanol, ethanol, n ‑propanol and n ‑butanol)/DMSO‑ d 6 , the tautomer distribution of d ‑fructose in methanol/DMSO‑ d 6 exhibited the shortest equilibration time (46 h) and the lowest concentration of β‑furanose (39.0%) at equilibrium. The fraction of fructofuranose (α‑furanose and β‑furanose) at equilibrium and time needed to reach equilibrium in branched chain alcohols/DMSO‑ d 6 obey the following order: 2‑propanol/DMSO‑ d 6 (62.2%, 320 h) > tert ‑butanol/DMSO‑ d 6 (61.6%, 307 h) > 2‑butanol/DMSO‑ d 6 (60.6%, 216 h) > isobutanol/DMSO‑ d 6 (57.8%, 134 h). For the diols/DMSO‑ d 6 , the time for the tautomer distribution of d ‑fructose to reach the equilibrium was found to be: 1,4‑butanediol/DMSO‑ d 6 (113 h) > 1,2‑propanediol/DMSO‑ d 6 (38 h) > ethylene glycol/DMSO‑ d 6 (36 h). For ethanol/DMSO‑ d 6 and methanol/DMSO‑ d 6 with respectively different volume ratios, the experimental results showed that the high concentration of ethanol or methanol increases the conversion rate of tautomers.
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高影响因子
POLYMER
·
2018
·
IF 3.483
Yanyun Li,Tao Jing,Gaofeng Xu,Jingzhi Tian,Mengyao Dong,Qian Shao,Bin Wang,Zhikang Wang,Yongjie Zheng,Changlong Yang,Zhanhu Guo
Three-dimensional magnetic graphene oxide-magnetite polyvinyl alcohol (3D-GO/PVA/Fe 3 O 4 ) nanocomposites were successfully prepared. The morphology was characterized and analyzed through scanning electron microscope (SEM) and transmission electron microscope (TEM). The chemical structure and the crystal structure were explored by X-ray powder diffraction (XPS), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction spectra (XRD). The magnetic property was obtained by vibrating sample magnetometer (VSM). The specific surface area and the average pore size were determined by Brunauer-Emmett-Teller (BET) and Barrett–Joyner–Halenda (BJH). The specific surface and the average pore size of 3D-GO/PVA/Fe 3 O 4 nanocomposites were 388.87 m 2 g -1 and 9.6 nm, and the higher specific surface indicated that the three-dimensional structure avoided the aggregation for GO sheets. The large saturation magnetization (M s ) of the nanocomposites of 30.5 emu/g enabled the easy cycling of the nanocomposites. The 3D-GO/PVA/Fe 3 O 4 nanocomposites exhibited better performance for porcine pancreatic lipase (PPL) enzyme immobilization. The maximum immobilization efficiency was 91%, and the enzyme immobilized 3D-GO/PVA/Fe 3 O 4 nanocomposites reached up to 90% of their activities. After 10 cycles of reuse, the activity of immobilized enzyme remained about 70.8% of the initial activity. The stability test revealed that the activity of immobilized enzyme remained up to 71.1% at 4 °C for 56 days.
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GREEN CHEMISTRY
·
2015
·Vol. 18
·期 6
·1738-1750
·
IF 8.02
Jiliang Ma,Linxin Zhong,Xinwen Peng,Runcang Sun
A simple and effective synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones and their derivatives from aldehydes, β-dicarbonyl compounds and urea or thiourea using D-xylonic acid both as a green solvent and an effective catalyst is described. Taking the environment and economy into account, the work presented here has the merits of environmental friendliness, easy operation, simple work-up, excellent yields and the avoidance of organic solvents and inexpensive catalysts. In addition, the good properties of D-xylonic acid have also been validated by the synthesis of 5-phenyl-1(4-methoxyphenyl)-3[(4-methoxyphenyl)-amino]-1H-pyrrol-2(5H)-one and 12-phenyl-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one. The synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR and melting point.
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危险品化学品经营许可证（带存储）