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POLYMER · 2016 · IF 3.586

Redox-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-lactic acid) for intracellular drug delivery

Qinglai Yang,Changyu He,Zhen Zhang,Lianjiang Tan,Bingya Liu,Zhenggang Zhu,Zhifeng Shao,Bing Gong,Yu-Mei Shen

Redox-responsive micelles self-assembled from triblock copolymers of poly( l -lactic acid)-poly(ethylene glycol)-poly( l -lactic acid) ( PLA-PEG-PLA) with double-disulfide linkage in the backbone were synthesized and characterized by proton nuclear magnetic resonance ( 1 H NMR) and size exclusion chromatography (SEC), in which both PEG ( M n  = 1000, 2000 and 4000 g mol −1 ) and PLA ( M n  = 1600 g mol −1 ) have different molecular weights respectively. The triblock copolymers PLA 3000 -PEG 2000 -PLA 3000 and PLA 3000 -PEG 4000 -PLA 3000 can self-assemble into flower-like micelles in aqueous media with average diameters 110 nm and 43 nm and lower critical micelle concentrations (CMC) 0.017 and 0.014 mg   mL −1 respectively compared with that of diblock copolymers. Moreover, in vitro drug release analyses indicated that reductive environment can result in triggered drug release profiles. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl- 2-H-tetrazolium bromide (MTT) assay in vitro showed no significant cytotoxicity as NIH 3T3 cells incubated in the micelles even when the concentrations up to 1000 μg/mL. Additionally fluorescence microscopy measurements and MTT assay demonstrated that the micelles exhibited a faster drug release and higher cellular proliferation inhibition due to the effect of intracellular reduction responsiveness compared with that of diblock copolymers. The above results suggest that the reduction-responsive, biodegradable and biocompatibility micelles could provide a platform to construct potential drug delivery systems for cancer therapy.

研究领域: 生物材料学 · 药剂学 · 肿瘤治疗
✓ 已验证 DOI 高影响因子
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RSC Advances · 2016 ·Vol. 6 ·期 21 ·17016-17022 · IF 3.289

Tyrosinase-catalyzed polymerization of L-DOPA (versus L-tyrosine and dopamine) to generate melanin-like biomaterials for immobilization of enzymes and amperometric biosensing

Mengzhen Dai,Ting Huang,Long Chao,Yueming Tan,Chao Chen,Wenhua Meng,Qingji Xie

Learning from nature emerges as one of the most promising ways to develop advanced functional materials and biodevices. Here, inspired by melanin formation, we report the tyrosinase (Tyr)-catalyzed polymerization of L-DOPA (versus L-tyrosine and dopamine) to immobilize enzymes for amperometric biosensing. The enzymatic polymerization is examined by UV-vis spectrophotometry, scanning electron microscopy and electrochemical methods. A poly(L-DOPA) (PD)-Tyr/glassy carbon electrode (GCE) prepared by casting an aqueous mixture of L-DOPA and Tyr on a GCE exhibits a linear cathodic amperometric response to catechol concentration from 0.4 to 57 μM (R2 = 0.997) with a sensitivity of 4.29 mA mM−1 cm−2 and a limit of detection (LOD) of 70 nM (S/N = 3). A PD-glucose oxidase (GOx)-Tyr/Pt electrode prepared by casting an aqueous mixture of L-DOPA, GOx and Tyr on a Pt electrode exhibits a linear anodic amperometric response to glucose concentration from 2 to 5700 μM (R2 = 0.998) with a sensitivity of 78.6 μA mM−1 cm−2 and a LOD of 0.1 μM (S/N = 3). The PD-based enzyme electrode shows better biosensing performance and higher bioactivity of the immobilized Tyr than those based on similarly biosynthesized poly(L-tyrosine) and polydopamine as well as well-established chitosan and Nafion systems, implying that the biosynthesized PD as a melanin-biomimetic material has promising application potential for biomacromolecular immobilization and biosensing.

✓ 已验证 DOI 高影响因子
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BIOMACROMOLECULES · 2012 · IF 5.479

Photoresponsive Poly(S-(o-nitrobenzyl)-l-cysteine)-b-PEO from a l-Cysteine N-Carboxyanhydride Monomer: Synthesis, Self-Assembly, and Phototriggered Drug Release

Gang Liu,Chang-Ming Dong

A photoresponsive S-(o-nitrobenzyl)-l-cysteine N-carboxyanhydride (NBC-NCA) monomer was for the first time designed, and the related poly(S-(o-nitrobenzyl)-l-cysteine)-b-poly(ethylene glycol) (PNBC-b-PEO) block copolymers were synthesized from the ring-opening polymerization (ROP) of NBC-NCA in DMF solution at 25 °C. Their molecular structures, physical properties, photoresponsive self-assembly, and drug release of PNBC-b-PEO were thoroughly investigated. The β-sheet conformational PNBC block within copolymers presented a thermotropic liquid crystal phase behavior, and the crystallinity of PEO block was progressively suppressed over the PNBC composition. The characteristic absorption peaks of these copolymers at about 310 and 350 nm increased over UV irradiation time and then leveled off, indicating that the o-nitrobenzyl groups were gradually photocleaved from copolymers until the completion of photocleavage. The PNBC-b-PEO copolymers self-assembled into spherical nanoparticles in aqueous solution, presenting a photoresponsive self-assembly behavior, together with a size reduction of nanoparticles after irradiation. The anticancer drug doxorubicin can be released in a controlled manner by changing the light irradiation time, which was induced by gradually photocleaving the PNBC core of nanoparticles. This work provides a facile strategy not only for the synthesis of photoresponsive polypeptide-based block copolymers but also for the fabrication of photoresponsive nanomedicine potential for anticancer therapy.

研究领域: 高分子化学 · 生物材料 · 药学
✓ 已验证 DOI 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Rational engineering and insight for a L-glutaminase activity reduced type II L-asparaginase from Bacillus licheniformis and its antileukemic activity in vitro

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.

CAS / MDL: 70-47-3 56-85-9 76-03-9
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Polymers · 2022 ·Vol. 14 ·期 17 ·3449 · IF 4.967

Using Cellulose-graft-Poly(L-lactide) Copolymers as Effective Compatibilizers for the Preparation of Cellulose/Poly(L-lactide) Composites with Enhanced Interfacial Compatibility

Fei Liu,Shan Lu,Weihong Cao,Juncheng Huang,Yi Sun,Yiting Xu,Meiling Chen,Haining Na,Jin Zhu

Cellulose-grafte-poly(L-lactide) (C-g-PLLA) copolymers synthesized in a CO2-switchable solvent are proposed for use as effective compatibilizers for the preparation of cellulose–PLLA composites with enhanced interfacial compatibility. The effect of the molar substitution (MSPLLA) of the grafted PLLA side chain in the C-g-PLLA copolymer and the feeding amount of this copolymer on the mechanical and thermal properties and hydrophilicity of the composites was investigated. The composites had a largely increased impact strength with the incorporation of the compatibilizer. With the increasing ofMSPLLAand the feeding amount of the copolymer, the resulting composites had an increased impact strength. When 5 wt% C-g-PLLA withMSPLLAof 4.46 was used as a compatibilizer, the obtained composite containing 20 wt% cellulose presented an impact strength equal to that obtained for the neat PLLA. The composites had a slightly decreased melting temperature and thermal decomposition temperature, but increased hydrophilicity due to the incorporation of the compatibilizer. This work suggests an effective method to improve the interfacial compatibility between cellulose and PLLA for the fabrication of fully bio-based composites with high performance.Keywords:cellulose;poly(L-lactide);composite;compatibilizer;CO2-switchable solvent

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Molecular Catalysis · 2022 · IF 5.089

An Effective Chemo-Enzymatic method with An Evolved L-Threonine Aldolase for Preparing L-threo-4-Methylsulfonylphenylserine Ethyl Ester of High Optical Purity

Li-Chao Wang,Lian Xu,Bing-Mei Su,Xin-Qi Xu,Juan Lin

L- threo -4-methylsulfonylphenylserine ethyl ester [(2 S , 3 R )- 1d ], a key building block of florfenicol which synthesized by esterification using ethanol and L- threo -4-methylsulfonylphenylserine [(2 S , 3 R )- 1b ] as substrates. L-threonine aldolase (LTA) is a promising biocatalyst for producing (2 S , 3 R )- 1b through a one-step process taking 4-Methylsulphonyl benzaldehyde ( 1a ) and glycine as substrates under the mild condition. However, the moderate C β -stereoselective blocked the industrial application of LTA. To address this issue, rational design by combination with prereaction state molecular dynamics (MD) simulation and per-residue energy decomposition algorithm are employed to engineer LTA for enhancing C β -stereoselective. As a result, a triple mutant N16A/E98S/Y314R (Mu3) is screened out to produce (2 S , 3 R )- 1b with 93.7% de and 90.2% conversion under the 300 mM 1a substrate loading. Furthermore, esterification is applied to synthesize (2 S , 3 R )- 1d with over 99% chiral purity and 99% product purity. The success of this study provides new insights for the rational design of LTA with improved C β -stereoselectivity and proves a chemo-enzymatic route for green synthesis of (2 S , 3 R )- 1d .

✓ 已验证 产品关联 DOI 高影响因子
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MOLECULES · 2018 ·Vol. 23 ·期 12 ·3377 · IF 3.098

Small Molecular Weight Aldose (d-Glucose) and Basic Amino Acids (l-Lysine, l-Arginine) Increase the Occurrence of PAHs in Grilled Pork Sausages

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

✓ 已验证 DOI PubMed 高影响因子
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BIOORGANIC CHEMISTRY · 2024 · IF 4.5

Exploiting the biocatalytic potential of co-expressed l-fucose isomerase and d-tagatose 3-epimerase for the biosynthesis of 6-deoxy-l-sorbose

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.

CAS / MDL: 367-93-1 8063-07-8
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2011 ·Vol. 173 ·期 1 ·241-247 · IF 2.578

Electrochemistry and voltammetric determination of L-tryptophan and L-tyrosine using a glassy carbon electrode modified with a Nafion/TiO2-graphene composite film

Fan Yang,Liu Jin-Hang,Lu Hai-Ting,Zhang Qin

We describe a glassy carbon electrode (GCE) modified with a film composed of Nafion and TiO 2 -graphene (TiO 2 -GR) nanocomposite, and its voltammetric response to the amino acids L-tryptophane (Trp) and L-tyrosine (Tyr). The incorporation of TiO 2 nanoparticles with graphene significantly improves the electrocatalytic activity and voltammetric response compared to electrodes modified with Nafion/graphene only. The Nafion/TiO 2 -GR modified electrode was used to determine Trp and Tyr with detection limits of 0.7 and 2.3 μM, and a sensitivity of 75.9 and 22.8 μA mM −1 for Trp and Tyr, respectively. The electrochemical sensor based on Nafion/TiO 2 -GR composite film modified GCE was presented. The integration of TiO 2 nanoparticles with graphene provides an efficient microenvironment to promote the electrochemical reaction of amino acids Trp and Tyr. The fabricated electrochemical sensor exhibits favorable analytical performance for Trp and Tyr, with high sensitivity, low detection limit and good reproducibility.

✓ 已验证 产品关联 DOI 高影响因子
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PHYTOCHEMISTRY · 2026 · IF 3.4

Candosins A-L: potential antiparkinsonian agents from Candolleomyces sp.

Tong-De Zhao,Xue-Qiong Yang,Wei Chen,Hua Xu,Yan-Wei Yin,Yun-Li Zhao,Ya-Bin Yang,Zhong-Tao Ding

Candolleomyces sp. showed anti-PD in mice, and in vitro neuroprotective effect. • Candosin B had an unprecedented spiral 6/6/6/5-fused tetracyclic backbone. • Candosins A, C were undescribed 6/6/7/5-fused tetracyclic diterpenoid skeletons. • Candosins B-E, G-I, K and L showed obvious neuroprotective effects. Three fractions of Candolleomyces sp. cultured on Chinese yam agar solid medium were tested for the neuroprotective activity against Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) with model mice. Assessments including in vivo open field test (OFT), α-synuclein (α-syn) and tyrosine hydroxylase (TH) expression, pathological examination, and in vitro neuroprotective effects revealed that the dichloromethane fraction exhibited anti-PD effect. The work led to the isolation of 12 undescribed guanacastane diterpenoids candosins A–L ( 1 − 12 ). Candosin B ( 2 ) was an unprecedented diterpenoid with 6/6/6/5-fused tetracyclic backbone containing one [5.5] spiro ring. Candosins A and C ( 1 and 3 ) were undescribed diterpenoid skeletons with 6/6/7/5-fused tetracyclic backbone containing a pyran ring, and a furan ring. The structures were elucidated according to the NMR, HRESIMS, and ECD spectra. Compounds 2 – 5 , 7 – 9 , 11 , and 12 exhibited significant neuroprotective effects on MPP  +  induced PC-12 cell injury, with viability ranging from 68.63% to 87.97%. The docking results indicated that active diterpenoids produced by fungus Candolleomyces sp. might exert a protective effect on PD through α-syn mediated signaling pathway. The dichloromethane fraction of Candolleomyces sp., cultured on Chinese yam agar solid medium, exhibited anti-PD activity, leading to the isolation of 12 previously undescribed guanacastane diterpenoids, candosins A–L ( 1 – 12 ). Molecular docking suggested that α-synuclein (α-syn) may serve as a potential molecular target for the neuroprotective effects of compounds 2 – 5 , 7 – 9 , 11 , and 12 . Download: Download high-res image (433KB) Download: Download full-size image

CAS / MDL: 23007-85-4 91374-20-8
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Catalysis Science & Technology · 2023 ·Vol. 13 ·期 13 ·3953-3962 · IF 5

Enzymatic hydrolysis of L-azetidine-2-carboxylate ring opening

Xuexia Xu,Qin Yang,Lanteng Wang,Jie Zheng,Yang Gu,Xiwen Xing,Jiahai Zhou

The L-proline analogue, L-azetidine-2-carboxylate (L-AZC), is of considerable interest both from biological and medicinal chemistry perspectives. It can be quickly involved in proteins and cause protein misfolding, disrupting the normal function of the protein. L-AZC can be biodegraded as the only carbon and nitrogen source by bacteria, and the hydrolysis on the ring opening of L-AZC has an effective practical detoxification function. We identified an L-AZC hydrolase from Novosphingobium sp. MBES04 (NsA2CH), which belongs to the haloacid dehalogenase-like superfamily and participates in cyclic amino acid metabolism. This enzyme has high substrate and stereospecificity for the hydrolysis of L-AZC. We determined the high-resolution crystal structures of NsA2CH in the form of apo- and covalent complexes with the reaction intermediate. Detailed biochemical, structural, and computational studies provide the molecular mechanism of the substrate and stereoselectivity of NsA2CH. Further bioinformatics analysis revealed 328 NsA2CH homologues (sequence identity more than 60%) widely distributed in bacteria. Our work provides the first structural insight into A2CH covalently complexed with the reaction intermediate. The results will enable the engineering of L-AZC to the building block of aminoglycoside antibiotics.

✓ 已验证 产品关联 DOI 高影响因子
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LWT-FOOD SCIENCE AND TECHNOLOGY · 2022 · IF 6.056

Biodegradable packaging films with ε-polylysine/ZIF-L composites

Lei Zhang,Ziyuan Wang,Yi Jiao,Zichen Wang,Xiuming Tang,Zhanxin Du,Zeyang Zhang,Shihai Lu,Changsheng Qiao,Jiandong Cui

Recent years, biobased polymer packaging film in food packaging has witnessed great developments. However, it is still a challenge to develop biodegradable packaging films with antimicrobial property and mechanical strength. Herein, agar and polyvinyl alcohol (PVA)/Chitosan (CS) packaging films with ε-polylysine/ZIF-L nanocomposites (ε-PL@ZIF-L) were developed for the first time. Due to the incorporation of the nanocomposite, UV/visible light barrier properties (the transmittance decreased by 10.9%) of the films were improved, and the elongation at break of the composite agar films were increased by 43.0%. In the antimicrobial assays, with 4% ε-PL@ZIF-L, the inhibition zone diameters against Bacillus subtilis were 10 times as compared with the pure PVA/CS film. Furthermore, compared with commercial PE film, agar films and PVA/CS films with 4% ε-PL@ZIF-L nanocomposites could provide long-term protection for strawberry to avoid the microbial infection and prolong the shelf life of the fruit at 25 °C. The results suggested that the agar and PVA/CS packaging films with ε-PL@ZIF-L nanocomposites could significantly behave as potent antibacterial material in food packaging and preservation systems.

✓ 已验证 产品关联 DOI 高影响因子
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