APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2013
·Vol. 97
·期 17
·7597-7605
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IF 3.689
Xia Jun,Xu Hong,Feng Xiaohai,Xu Zhaoxian,Chi Bo
Poly(ε- l -lysine) (ε-PL) producer strain Streptomyces albulus PD-1 secreted a novel polymeric substance into its culture broth along with ε-PL. The polymeric substance was purified to homogeneity and identified. Matrix-assisted laser desorption ionization-time of flight mass spectrometry and nuclear magnetic resonance spectroscopy as well as other analytical techniques revealed that the substance was poly( l -diaminopropionic acid) (PDAP). PDAP is an l -α,β-diaminopropionic acid oligomer linking between amino and carboxylic acid functional groups. The molecular weight of PDAP ranged from 500 to 1500 Da, and no co-polymers composed of l -diaminopropionic acid and l -lysine were present in the culture broth. Compared with ε-PL, PDAP exhibited stronger inhibitory activities against yeasts but weaker activities against bacteria. ε-PL and PDAP co-production was also investigated. Both ε-PL and PDAP were synthesized during the stationary phase of growth, and the final ε-PL and PDAP concentration reached 21.7 and 4.8 g L -1 , respectively, in fed-batch fermentation. Citric acid feeding resulted in a maximum ε-PL concentration of 26.1 g L -1 and a decrease in the final concentration of PDAP to 3.8 g L -1 . No studies on ε-PL and PDAP co-production in Streptomyces albulus have been reported previously, and inhibition of by-products such as PDAP is potentially useful in ε-PL production.
研究领域:
微生物学
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生物化学
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分子生物学
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Journal of Pharmaceutical Analysis
·
2026
·
IF 11.2
Man Zhang,Shanshan Zhai,He Gao,Tong Sun,Kaixin Liu,Wenshuang Wang,Yuanyuan Hou,Gang Bai
Acute pulmonary inflammation, a major cause of morbidity and mortality, involves complex immune responses and increased vascular permeability. Conventional imaging techniques for assessing pneumonia and monitoring vascular leakage have limitations in spatial resolution and practicality. Rhodamine B-conjugated poly-L-lysine (RhB-PLL) self-assembled nanoparticles (NPs) were synthesized for targeting mitochondria and sensing vascular permeability. Dynamic spatiotemporal imaging analysis stratifies the progression of acute pneumonia into four distinct stages. Six phosphatidylcholine metabolites, exhibiting stage-dependent variations, were proposed as potential biomarkers to support RhB-PLL detection. Subsequently, Fuzheng Jiedu decoction (FZJD) was used as a model to validate the rationale of syndrome-specific treatment for pneumonia. Three simplified prescriptions derived from FZJD showed unique advantages at different stages. Xiaochaihu decoction (XCH) relieved inflammation and oxidative stress in mild to moderate cases; Sanren decoction (SR) reduced vascular leakage and prevented pulmonary edema in moderate to severe cases; Maxingshigan decoction (MXSG) improved mitochondrial function, prevented microcirculatory disorders in severe to critical cases. The combined prescription, FZJD, mitigated disease progression in mild to moderate cases and demonstrated the benefits of overall intervention. This conclusion was further substantiated by metabolomics cluster analysis. Real-time RhB-PLL multimodal imaging enables precise visualization and detection of inflammation progress, facilitates therapy assessment, and enhances the understanding of multicomponent drug combinations.
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JOURNAL OF POLYMER RESEARCH
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2022
·Vol. 29
·期 5
·1-12
·
IF 3.061
Hu Chunwang,Wei Hongliang,Hua Bingyan,Zhang Yaqi,Wang Gang,Shen Yanmin,Niu Yongsheng
Drug- controlled delivery can effectively avoid excessive drug use and improve the utilization rate of drugs and reduce the harm of drugs to the body. Herein, a novel poly(α-L-lysine)-based interpenetrating network (IPN) hydrogel with thermo/pH sensitivity was fabricated by synchronous free-radical polymerization and amine-anhydride click reaction in one pot. The hydrogels were characterized by FTIR, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The IPN hydrogels well integrated thermo-sensitivity and pH-sensitivity of two single-network hydrogels. The experimental results showed that the IPN hydrogel exhibited different swelling properties at different pH and temperatures. Finally, the anticancer drug 5-fluorouracil (5-Fu) was chosen as a model drug to investigate the controlled release behavior of the hydrogel. The study showed that the release behavior of 5-Fu from the IPN hydrogel depended on temperature and pH changes, which followed the Korsmeyer-Peppas kinetic model. The IPN hydrogel is expected to be a candidate material for drug sustained-release carriers.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2022
·
IF 7.088
Xing-Rong Wang,Shuai Wang,Hong-Xia Mu,Kai-Yan Xu,Xue-Ting Wang,Jian-Tao Shi,Qi-Hang Cui,Li-Wen Zhang,Shi-Wu Chen
VEGFR-2 is an attractive therapeutic target for antitumor drug research by blocking tumor angiogenesis and PROTAC provides a new technology for targeted protein knockout. Herein, a library of novel VEGFR-2-PROTAC degraders were rationally designed and synthesized based on the Lys residue region on the surface of VEGFR-2 protein using protein structure-based drug design strategy. Among them, P7 exhibited preferable antitumor activity against HGC-27 cells and less toxic to human normal HUVEC, HEK293T and GES-1 cells in vitro , as well as the potent degradation activity of VEGFR-2 protein in HGC-27 cells (DC 50 : 0.084 ± 0.04 μM, D max : 73.7%) and HUVEC cells (DC 50 : 0.51 ± 0.10 μM, Dmax: 76.6%). Additionally, P7 degraded VEGFR-2 protein by the formation of ternary complex and the ubiquitin proteasome pathway in HGC-27 cells. Furthermore, P7 shortened the half-life of VEGFR-2 protein synthesis and had no inhibitory effect on the expression of VEGFR-2 mRNA in HGC-27 cells. Moreover, P7 inhibited the colony formation, migration and invasion of HGC-27 cells in a time- and dose-dependent manner, and meanwhile induced G 2 /M phase cycle arrest and apoptosis . All the results demonstrated that P7 could be as a promising VEGFR-2-PROTAC degrader for gastric cancer therapy.
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CHEMICAL ENGINEERING JOURNAL
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2023
·
IF 15.1
Kangyu Liu,Bingzhang Shao,Haichao Liu,Jinlong He,Aiguo Zheng,Genghong Li,Bo Zheng,Zeyang Li,Wei Liu,Xuefeng Li,Baoning Zong
Antibacterial monomers are prerequisites for synthesizing antibacterial polymers, especially during the current COVID-19 pandemic. Dimethyl-protected cyclic lysine (DMCL) is a promising functional monomer for nylon-6 based self-cleaning antibacterial polymers. However, the production of DMCL still faces formidable challenges, such as harsh reaction conditions and low catalyst activities. In this study, we developed a Pd/ m -Al 2 O 3 -Si catalyst, which exhibited high efficiency in converting α -amino- ε -caprolactam ( α -ACL) to DMCL, affording a yield of as high as 97.1% at 100 °C and 1 MPa H 2 . The lack of Brönsted acid sites on the catalyst surface facilitated the formation of DMCL and suppressed undesirable hydrolysis or cracking by-products from the lactam-based reactant. The recycled experiments showed that Pd/ m -Al 2 O 3 -Si performed excellent stability and physical strength with essentially no damage to its microspheres after the reaction. The nylon‑6 copolymers produced from the as-synthesized DMCL exhibited similar structure and thermal stability with pure nylon-6, showing great potential in synthesizing the self-cleaning antibacterial polymers. This work provides a sustainable and efficient method for producing DMCL and other lysine-based antibacterial monomers, showing a great prospect for the utilization of bio-based chemicals in synthesizing functional polymers.
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MOLECULES
·
2018
·Vol. 23
·期 12
·3377
·
IF 3.098
Wen Nie,Ke-zhou Cai,Yu-zhu Li,Shuo Zhang,Yu Wang,Jie Guo,Cong-gui Chen,Bao-cai Xu
(1) Background: Amino acids and carbohydrates are widely used as additives in the food industry. These compounds have been proven to be an influencing factor in the production of chemical carcinogenic compounds polycyclic aromatic hydrocarbons (PAHs). However, the effect of the properties of the amino acids and carbohydrates on the production of PAHs is still little known. (2) Methods: We added different (i) R groups (the R group represents an aldehyde group in a glucose molecule or a ketone group in a fructose molecule); (ii) molecular weight carbohydrates; (iii) polarities, and (iv) acid-base amino acids to pork sausages. The effects of the molecular properties of carbohydrates and amino acids on the formation of PAHs in grilled pork sausages were investigated. (3) Results: The results showed that a grilled sausage with aldehyde-basedd-glucose was capable of producing more PAHs than a sausage with keto-basedd-fructose. A higher PAH content was determined in the grilled pork sausage when the smaller molecular weight,d-glucose, was added compared with the sausage where the larger molecular weight, 4-(α-d-glucosido)-d-glucose and cellulose were added. The addition of basic amino acids (l-lysine,l-arginine) was capable of producing more PAHs compared with the addition of acidic amino acids (l-glutamic acid,l-aspartate). When amino acid containing a benzene ring was added, a smaller volume of PAHs was produced compared with the addition of other amino acids. (4) Conclusions: Our study suggests that systematic consideration of molecule properties is necessary when using food additives (amino acids and carbohydrates) for food processing.Keywords:amino acids;carbohydrates;acidity;polarity;molecular weight
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RSC Advances
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2019
·Vol. 9
·期 27
·15162-15170
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IF 3.049
Yuting Wang,Huiyu Hu,David Julian McClements,Shaoping Nie,Mingyue Shen,Chang Li,Yousheng Huang,Jie Chen,Maomao Zeng,Mingyong Xie
Lysine-derived advanced glycation end-products (AGEs), including Nε-carboxymethyllysine (CML), Nε-carboxyethyllysine (CEL) and pyrraline, are prevalent in processed foods. The impact of lipids on AGE formation is still contentious and most of our current knowledge is based only on CML. Little is known about how lipids impact the formation of CEL and pyrraline, or their involvement in formation pathways. This study investigated the effect of lipids (fatty acids and triglycerides) on the formation of CML, CEL and pyrraline simultaneously in model systems subjected to frying temperature. The results showed the presence of the lipids promoted the formation of CML, CEL and pyrraline. The promotion effects on CML and CEL were not dependent on the unsaturation degree and addition level (50, 100 or 150 μmol) of lipid, while pyrraline formation depended on lipid type (fatty acids vs. triglycerides) and level. The concentration of CML and CEL was statistically correlated with the concentration of glyoxal (GO) and methylglyoxal (MGO), respectively. The pyrraline concentration was statistically correlated with fructoselysine concentration. These results suggested that lipids promote the formation of lysine-derived AGEs by impacting the generation of Amadori products and α-dicarbonyl compounds. This information may be useful for optimizing the formulation and processing conditions to create tastier and healthier foods.
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PHYTOTHERAPY RESEARCH
·
2024
·
IF 6.1
Meng Wang,Qiurui Li,Shang Wang,Ling Zuo,Yang Hai,Su Yuan,Xuezhi Li,Xuekuan Huang,Congwen Yang,Ling Yao,Wenfu Cao,Guoqing Zuo,Jianwei Wang
Tubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high-glucose-stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta-hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl-transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high-glucose-induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress-associated proximal tubular injury by upregulating CPT1A-mediated K99 succinylation of HSD17B10 to maintain RNase P activity.
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ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Xiaoyan Zhou,Qianqian Zheng,Changyong Wang,Jiake Xu,Jian-Ping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.
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Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 7
·1284-1295
·
IF 4.872
Min Tang,Haiqing Dong,Yongyong Li,Tianbin Ren
Dendrimer catiomers like dendrigraft poly-L-lysine (DGL) have been very popular vectors for gene delivery recently; however, they generally suffer from serious cytotoxicity for high density of positive charge. PEGylated DGL engineered using the PEG cleavable mechanism (DGL(R)-SS-mPEG) was first developed as a non-viral gene vector for cancer intervention. Cleavable PEGylation of the DGL catiomer in tumor relevant glutathione (GSH) conditions enables us to dramatically decrease the cytotoxicity as well as to promote the intracellular release and expression of the genetic payload. Like DGL, DGL(R)-SS-mPEG is capable of efficiently complexing with plasmid DNA (pDNA) to afford homogeneous compact nano-complexes. Those gene carrying nanostructures could be stably dispersed in the regular serum medium without GSH, but with fast PEG dis-assembly if subject to 10 mM GSH. Compared with the non-cleavable counterpart, PEG-cleavable dendrigraft poly-L-lysine exhibited significantly higher enhanced green fluorescence protein (EGFP) expression against 293T cells. By using small interfering RNA (siRNA-VEGF) as the therapeutic gene payload, the complex nanoparticles demonstrated the pronounced inhibition effect on cell growth in vitro and tumor growth in vivo. The promising results revealed a universal strategy to balance disadvantages and advantages of dendrimer catiomers for future non-viral gene delivery vector.
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Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Beibei Hu,Yue Yuan,Yun Yan,Xiaoping Zhou,Yue Li,Qiming Kan,Sanming Li
A novel bolaamphiphile surfactant N , N ′-(dodecane-1, 12-diyl) bis (2,6-diaminohexanamide) (DADL) was designed and synthesized using l -lysine and 1,12-diaminododecane as the hydrophilic and hydrophobic part, respectively. After separation and purification, the structure of the synthetic bolaamphiphile surfactant was verified by FTIR, MS and 1 H NMR. The synthetic bolaamphiphile was able to self-assemble to form vesicles. After formulation screening, vesicles loaded with 5-Fluorouracil (5-Fu) were prepared with Tween 60 and DADL by sonication and were examined by dynamic light scattering and transmission electron microscopy. Micro-FTIR was applied to investigate the conformation of the bola molecules within the vesicle membrane. The release profile of the vesicles showed a pH-sensitive and sustained release. No significant toxicity was observed in an in vitro cell viability assay. The antitumor efficacy of the 5-Fu-loaded vesicles on H 22 tumor-bearing mice was remarkably high due to the EPR effects. These results show that our novel bolaamphiphile derived from lysine has excellent potential as a pH-sensitive drug carrier.
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Biosensors-Basel
·
2024
·Vol. 14
·期 3
·121
·
IF 4.9
Chuanxiang Zhang,Song Li,Lingxiao Tang,Shuo Li,Changchun Hu,Dan Zhang,Long Chao,Xueying Liu,Yimin Tan,Yan Deng
Development of an efficient technique for accurate and sensitive dibutyl phthalate (DBP) determination is crucial for food safety and environment protection. An ultrasensitive molecularly imprinted polymers (MIP) voltammetric sensor was herein engineered for the specific determination of DBP using poly-l-lysine/poly(3,4-ethylenedioxythiophene)/porous graphene nanocomposite (PLL/PEDOT−PG) and poly(o-phenylenediamine)-imprinted film as a label-free and sensing platform. Fabrication of PEDOT−PG nanocomposites was achieved through a simple liquid–liquid interfacial polymerization. Subsequently, poly-l-lysine (PLL) functionalization was employed to enhance the dispersibility and stability of the prepared PEDOT−PG, as well as promote its adhesion on the sensor surface. In the presence of DBP, the imprinted poly(o-phenylenediamine) film was formed on the surface of PLL/PEDOT−PG. Investigation of the physical properties and electrochemical behavior of the MIP/PLL/PEDOT−PG indicates that the incorporation of PG into PEDOT, with PLL uniformly wrapping its surface, significantly enhanced conductivity, carrier mobility, stability, and provided a larger surface area for specific recognition sites. Under optimal experimental conditions, the electrochemical response exhibited a linear relationship with a logarithm of DBP concentration within the range of 1 fM to 5 µM, with the detection limit as low as 0.88 fM. The method demonstrated exceptional stability and repeatability and has been successfully applied to quantify DBP in plastic packaging materials.
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