International Journal of Nanomedicine
·
2014
·
IF 4.195
Ziming Zhao,Yu Wang,Jin Han,Keli Wang,Dan Yang,Yihua Yang,Qian Du,Yuanjian Song,Xiaoxing Yin
The aim of this work was to design, synthesize, and characterize self-assembled micelles based on polypeptides as a potential antitumor drug carrier. Amphiphilic poly( l -phenylalanine)- b -poly( l -serine) (PFS) polypeptides were obtained through the polymerization of N -carboxyanhydride. As a novel hydrophilic segment, poly( l -serine) was utilized to enhance tumor targeting due to a large demand of tumors for serine. PFS could self-assemble into micelles with an average diameter of 110–240 nm and a slightly negative charge. PFS polypeptides adopted random coil in pH 7.4 phosphate-buffered saline and could partly transform to α-helix induced by trifluoroethanol. PFS micelles with a low critical micelle concentration of 4.0 μg mL −1 were stable in pH 5–9 buffers and serum albumin solution. PFS micelles had a loading capacity of 3.8% for coumarin-6 and exhibited a sustained drug release. Coumarin-6 loaded rhodamine B isothiocyanate-labeled PFS micelles were incubated with Huh-7 tumor cells to study the correlation between drugs and carriers during endocytosis. The uptake of drugs was consistent with the micelles, illustrating that the intracellular transport of drugs highly depended on the micelles. PFS micelles diffused in whole cytoplasm while coumarin-6 assumed localized distribution, suggesting that the micelles could release the loaded drugs in particular areas. The internalization mechanism of PFS micelles was involved with clathrin-mediated endocytosis and macropinocytosis. Excess serine inhibited the uptake of PFS micelles, which demonstrated that serine receptors played a positive role in the internalization of PFS. The more interesting thing was that the uptake inhibition impacted on normal cells but not on tumor cells at the physiological concentration of serine. The difference in the uptake of PFS micelles was fourfold as high between the tumor cells and the normal cells, which indicated that PFS micelles had good tumor targeting in vitro. In conclusion, PFS micelles reported in this work were a promising drug delivery system for tumor targeting therapy.
研究领域:
药学
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生物医学工程
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纳米技术
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癌症研究
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DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2024
·
IF 8.1
Zikang Qin,Yulei Ma,Wentao Du,Jing Wei,Jia Song,Xinyue Fan,Lu Yao,Lin Yang,Yuanfa Zhuang,Wenju Jiang,Zhongde Dai
Amine-functionalized Metal-Organic Frameworks (MOFs) stand out as highly promising materials in membrane separation technology. Nevertheless, the incorporation of amine-functionalized additives may lead to uncontrollable alterations in MOF morphology. Two intact blade-like MOFs (PEI (Polyethylenimine)-ZIF-L and PAMAM (Polyamidoamine)-ZIF-L) were successfully synthesized by controlling the conditions and then introduced into Pebax 2533 to fabricate Mixed Matrix Membranes (MMMs). Hydrogen bonding and other interactions with Pebax can be formed by PEI-ZIF-L and PAMAM-ZIF-L to enhance interfacial compatibility. Simultaneously, a reversible reaction with CO 2 molecules can be undergone by the amine groups, resulting in facilitated transport in MMMs. The CO 2 separation performance of the MMMs is enhanced by this process, with the facilitation being more pronounced under humid conditions. Under humid conditions, the CO 2 permeabilities of Pebax-PEI-ZIF-L (2 wt%) and Pebax-PAMAM-ZIF-L (2 wt%) MMMs were 639.4 Barrer and 702.7 Barrer, respectively, while the CO 2 /N 2 selectivities were 26.68 and 24.35, respectively. Both permeability and selectivity exhibited a significant increase of 200% and 130%, respectively, compared to pure Pebax. Furthermore, the MMMs demonstrated excellent long-term stability during 72 h of continuous operation in a humid environment, showcasing significant potential for industrial applications, particularly in humid flue gas carbon capture.
研究领域:
膜科学
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材料科学
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环境工程
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化学工程
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DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2017
·Vol. 41
·期 24
·15216-15228
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IF 3.269
Xiaoqing Zeng,Lei Zhang,Jidong Yang,Yuan Guo,Yunmei Huang,Haiyan Yuan,Yongsheng Xie
In this report, water-soluble carbon dots (CDs) with stable fluorescence (FL) were designed and synthesized by using environment-friendly reduced L-glutathione (GSH) as the precursor and ethylenediamine (EDA) as the passivating agent through a one-step hydro-thermal method. The CDs, with bright blue FL, had the quantum yield (QY) of 40% and showed excellent monodispersity and solubility in water. The FL intensity was remarkably enhanced when a racemic modification of L-/D-arginine (Arg) was added into the CDs solution. Therefore, the CDs could be considered as a sensitive probe for the detection of Arg. Under optimized conditions, the CDs exhibited a linear fluorescence response in the range of 3–124 μM (R2 = 0.9987) Arg with the detection limit of 2.85 × 10−8 M. In addition, no evident difference was observed when comparing the FL results of L-Arg and D-Arg. Therefore, this method could not be used in the chiral recognition of two enantiomers. Under optimum conditions, the mechanism and the reasons for the enhancement of FL were investigated. The developed method exhibited great stability, selectivity and accuracy in determining the Arg content in human urine sample and the recovery range was from 97.0% to 102.2%. Thus, our proposed method has potential application in biological molecular recognition.
研究领域:
分析化学
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生物化学
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医学诊断
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DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2023
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IF 4.4
Yu-Han Geng,Yu Xin,Jing Du,Ming-Yi Cui,Yuan-Yuan Liu,Le-Xi Zhang,Bin Ding
Chirality is a ubiquitous phenomenon in nature and has attracted wide attention in the biomedicine, pharmaceutics and biosensing research fields. Enantiomeric recognition of chiral compounds, especially chiral drugs and chiral amino acids, is important for human health and nutrition. In this work, through the encapsulation of L-His&R6G (L-His = L-Histidine; R6G = Rhodamine 6G) into MOF@MOF framework ZIF-67@ZIF-8, composited material L-His&R6G@ZIF-67@ZIF-8 can be obtained. Additionally, through the etching process, a unique yolk-shell ZIF-8 chiral composite optical sensors L-His&R6G@ZIF-8 ( 1 ) can be successfully prepared. Photo-luminescent (PL) experiment also reveals that 1 can highly sensitively detect L-Proline (L-Pro) through the “turn-on” detection strategy (K BH = 1.22 × 10 4 M −1 and detection limit 1.9 μM). Further yolk-shell L-His&R6G@ZIF-8-based fabricate flexible mixed-matrix membranes has been prepared using doctor-blading technique, which show significant fluorescence enhancement effect under ultraviolet lamp. This work also provides the unique example of preparing chiral yolk-shell framework composite sensors, which have broad application in chiral sensing area.
研究领域:
生物医学
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药学
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生物传感
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材料科学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2022
·
IF 5.307
Yudong Yin,Lixin Sheng,Juzheng Zhang,Liqiong Zhang,Jingjing Liu,Xiaoan Wen,Yanghan Liu,Yang Si,Keguang Cheng
Extensive research effort has been put in pentacyclic triterpenoids due to their numerous biological activities. However, their poor water solubility and low oral bioavailability limit their antitumor effects in vivo . To address these issues, 37 triterpenoid acid derivatives linked to l -phenylalanine or l -proline were designed and synthesized in this study. Structure-activity relationship (SAR) studies found two promising glycyrrhetinic acid (GA) derivatives 11 and 16. Compound 11 was obtained by C3-OH esterification and C30-COOH modification with l -phenylalanine while 16 was obtained by attaching C3-OH with l -phenylalanine. Compounds 11 and 16 exhibit up to 48- and 120-fold improvement respectively compared with the IC 50 values of naturally occurring GA in the cellular assay. Fluorescence microscope and flow cytometric analysis suggested that both compounds 11 and 16 increased the content of ROS and Ca 2+ in cancer cells, decreased mitochondrial membrane potential (JC-1), and activated the regulator caspase-3/8/9 to trigger cell apoptosis. RNA-seq analysis and western blot analysis indicated that compounds 11 and 16 may promote apoptosis by upregulating the functions of pro-apoptotic factors while inhibiting the proteasome activity.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
MOLECULES
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2022
·Vol. 27
·期 18
·6088
·
IF 4.927
Ke Shun Hu,Chong Le Chen,Huan Ru Ding,Tian Yu Wang,Qin Zhu,Yi Chen Zhou,Jia Min Chen,Jia Qi Mei,Sheng Hu,Jun Huang,Wei Rui Zhao,Le He Mei
Salvianic acid A (SAA), as the main bioactive component of the traditional Chinese herbSalvia miltiorrhiza, has important application value in the treatment of cardiovascular diseases. In this study, a two-step bioprocess for the preparation of SAA froml-DOPA was developed. In the first step,l-DOPA was transformed to 3,4-dihydroxyphenylalanine (DHPPA) using engineeredEscherichia colicells expressing membrane-bound L-amino acid deaminase fromProteus vulgaris.After that, the unpurified DHPPA was directly converted into SAA by permeabilized recombinantE. colicells co-expressingd-lactate dehydrogenase fromPediococcus acidilacticiand formate dehydrogenase fromMycobacterium vaccaeN10. Under optimized conditions, 48.3 mM of SAA could be prepared from 50 mM ofl-DOPA, with a yield of 96.6%. Therefore, the bioprocess developed here was not only environmentally friendly, but also exhibited excellent production efficiency and, thus, is promising for industrial SAA production.Keywords:salvianic acid A;l-DOPA;membrane-boundl-amino acid deaminases;biocatalysis;molecular biology;biological engineering
研究领域:
生物技术
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药学
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生物化工
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2021
·
IF 3.196
Yujing Bian,Xun Zhang,Zhenqi Zhu,Bin Yang
To date, it is challengeable to clearly identify and accurately characterize molecular vibrational modes of an amino acid and its hydrate. In this work, the terahertz absorption spectra of L -Lysine (Lys) and L -Lysine hydrate (Lys·H 2 O) have been measured by terahertz time-domain spectroscopy (THz-TDS) at the range of 0.3–2.5 THz under room temperature. The structural changes of Lys and Lys·H 2 O are sensitively observed by THz spectroscopy. Based on density functional theory (DFT), the vibrational frequencies of Lys and Lys·H 2 O are analyzed, the Lys single molecule model and the most optimal Lys·H 2 O single molecule model are established. The collective vibrational modes of Lys and Lys·H 2 O have been identified by potential energy distribution (PED) analysis and molecular vibrational animation of GaussView. The results demonstrate that the collective vibrational modes of Lys and Lys·H 2 O at various frequencies are originated from the dihedral torsion or the bond angle bend of different molecular chains in a single molecule, which drives the vibrations of related groups. Therefore, the combination of THz-TDS technology and PED analysis opens up an opportunity for identifying Lys and its hydrate, which provides a theoretical reference for studying vibrational modes of biomolecules.
研究领域:
生物物理学
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光谱学
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理论化学
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DOI
高影响因子
BIORESOURCE TECHNOLOGY
·
2024
·
IF 9.7
Jing Wang,Min Du,Xin Wang,Junchen He,Alei Zhang,Kequan Chen
To achieve industrial-scale putrescine production, a high efficient bio-synthesis of putrescine involving arginase (ARG, EC 3.5.3.1) and L-ornithine decarboxylase was evaluated here. Among the four arginases tested, ARG BT from Bos Taurus showed the highest activity (1966 U/mg). Compared to the L-arginine decarboxylase (ADC) pathway, the strain expressing ARG BT and L-ornithine decarboxylase (SpeC) produced 28.7 g/L putrescine, a 38.6 % increase. Two pyridoxal phosphate (PLP) salvage pathways were evaluated, and the strain BL-P Tac -PdxK co-expressed pyridoxal kinase (PdxK) performed better. D-Glucose was used as the co-substrate to improve the putrescine titer further. Under optimal conditions, 43.6 g/L putrescine was produced from 87.1 g/L L-arginine, and 76 g/L putrescine was synthesized on a 0.5 L scale. Using L-arginine fermentation broth (60 g/L) as the substrate, a titer of 30 g/L putrescine was achieved. This efficient biotransformation process presented here enables feasible industrial-scale putrescine production.
研究领域:
生物工程
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微生物学
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DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2021
·
IF 5.221
Zhu Wen-Yuan,Niu Kun,Liu Peng,Fan Yu-Hang,Liu Zhi-Qiang,Zheng Yu-Guo
L-methionine is an important natural amino acid with broad application prospects. A novel gene encoding the enzyme with the ability to catalyze O-succinyl-L-homoserine (OSH) to L-methionine was screened and characterized. The recombinant O-succinyl-L-homoserine sulfhydrylase from Thioalkalivibrio sulfidiphilus (tsOSHS) exhibited maximum activity at 35°C and pH 6.5. OSHS displayed an excellent thermostability with a half-life of 21.72 h at 30°C. Furthermore, the activity of OSHS increased 115% after Fe2+ added. L-methionine was obtained with a total yield reaching 42.63 g/L under the concentration of O-succinyl-L-homoserine 400 mM (87.6 g/L). These results indicated that OSHS is a potential candidate for applying in the large-scale bioproduction of L-methionine.
研究领域:
生物化学
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微生物学
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生物技术
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DOI
PubMed
高影响因子
NATURE BIOTECHNOLOGY
·
2021
·Vol. 39
·期 12
·1548-1555
·
IF 54.908
Fan Chuyao,Deng Qiang,Zhu Ting F.
Natural DNA is exquisitely evolved to store genetic information. The chirally inverted l -DNA, possessing the same informational capacity but resistant to biodegradation, may serve as a robust, bioorthogonal information repository. Here we chemically synthesize a 90-kDa high-fidelity mirror-image Pfu DNA polymerase that enables accurate assembly of a kilobase-sized mirror-image gene. We use the polymerase to encode in l -DNA an 1860 paragraph by Louis Pasteur that first proposed a mirror-image world of biology. We realize chiral steganography by embedding a chimeric d -DNA/ l -DNA key molecule in a d -DNA storage library, which conveys a false or secret message depending on the chirality of reading. Furthermore, we show that a trace amount of an l -DNA barcode preserved in water from a local pond remains amplifiable and sequenceable for 1 year, whereas a d -DNA barcode under the same conditions could not be amplified after 1 day. These next-generation mirror-image molecular tools may transform the development of advanced mirror-image biology systems and pave the way for the realization of the mirror-image central dogma and exploration of their applications.
研究领域:
分子生物学
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合成生物学
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生物技术
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信息存储
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Muhammad Waheed Iqbal,Xinrui Tang,Tahreem Riaz,Shahid Mahmood,Yufei Zhang,Mei Zhao,Junhua Yun,Jia Li,Xianghui Qi
6-Deoxy- l -sorbose (6-DLS) is an imperative rare sugar employed in food, agriculture, pharmaceutical and cosmetic industeries. However, it is a synthetic and very expensive rare sugars, previously synthesized by chemo-enzymatic methods through a long chain of chemical processes. Recently, enzymatic synthesis of rare sugars has attracted a lot of attention due to its advantages over synthetic methods. In this work, a promising approach for the synthesis of 6-DLS from an inexpensive sugar l -fucose was identified. The genes for l -fucose isomerase from Paenibacillus rhizosphaerae (Pr-LFI) and genes for d -tagatose-3-epimerase from Caballeronia fortuita (Cf-DTE) have been used for cloning and co-expression in Escherichia coli , developed a recombinant plasmid harboring pANY1-Pr-LFI/Cf-DTE vector. The recombinant co-expression system exhibited an optimum activity at 50 °C of temperature and pH 6.5 in the presence of Co 2+ metal ion which inflated the catalytic activity by 6.8 folds as compared to control group with no metal ions. The recombinant co-expressed system was stable up to more than 50 % relative activity after 12 h and revealed a melting temperature (T m ) of 63.38 °C exhibiting half-life of 13.17 h at 50 °C. The co-expression system exhibited, 4.93, 11.41 and 16.21 g/L of 6-DLS production from initial l -fucose concentration of 30, 70 and 100 g/L, which equates to conversion yield of 16.44 %, 16.30 % and 16.21 % respectively. Generally, this study offers a promising strategy for the biological production of 6-DLS from an inexpensive substrate l -fucose in slightly acidic conditions with the aid of co-expression system harboring Pr-LFI and CF-DTE genes.
研究领域:
生物技术
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酶学
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生化工程
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食品科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Yawen Zhou,Juan Shen,Huibing Chi,Xiaoyu Zhu,Zhaoxin Lu,Fengxia Lu,Ping Zhu
Type II L-asparaginase (ASNase) has been approved by the FDA for treating acute lymphoid leukemia (ALL), but its therapeutic effect is limited by low catalytic efficiency and L-glutaminase (L-Gln) activity. This study utilized free energy based molecular dynamics calculations to identify residues associated with substrate binding in Bacillus licheniformis L-asparaginase II (BLASNase) with high catalytical activity. After saturation and combination mutagenesis , the mutant LGT (74 L/75G/111 T) with intensively reduced l -glutamine catalytic activity was generated. The l -glutamine/L-asparagine activity (L-Gln/L-Asn) of LGT was only 6.6 % of parent BLASNase, whereas the L-asparagine (L-Asn) activity was preserved >90 %. Furthermore, structural comparison and molecular dynamics calculations indicated that the mutant LGT had reduced binding ability and affinity towards l -glutamine. To evaluate its effect on acute leukemic cells, LGT was supplied in treating MOLT-4 cells. The experimental results demonstrated that LGT was more cytotoxic and promoted apoptosis compared with commercial Escherichia coli ASNase. Overall, our findings firstly provide insights into reducing l -glutamine activity without impacting L-asparagine activity for BLASNase to possess remarkable potential for anti-leukemia therapy.
研究领域:
生物化学
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药理学
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分子生物学
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癌症研究
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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）