NEW JOURNAL OF CHEMISTRY
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2021
·Vol. 45
·期 6
·3193-3201
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IF 3.591
Lianglin Zhang,Shuwei Lin,Yi Li,Baozong Li,Yonggang Yang
Four Ala–Ala dipeptides with a semi-perfluoroalkyl chain were synthesized. The intermolecular hydrogen bonding among amide groups and carboxyl groups as well as the hydrophobic association of semi-perfluoroalkyl chains drove the self-assembly of dipeptides. Homochiral dipeptides were able to self-assemble into coiled nanoribbons in a mixed solvent of DMSO/H2O (5/5, v/v), while entangled twisted nanofibers formed for heterochiral ones in a mixed solvent of DMSO/H2O (4/6, v/v). The handedness of self-assemblies and the stacking chirality of phenylene groups were controlled by the chirality of the alanine residue at the C-terminal. The vibration circular dichroism investigation indicated that the helicity of the semi-perfluoroalkyl chain was controlled by the handedness of dipeptide self-assemblies. The X-ray diffraction study showed that homochiral and heterochiral dipeptides underwent distinct molecular packing during the self-assembly. Our results clearly demonstrated that, through supramolecular self-assembly, the chirality transferred from the amino acid building block to the self-assemblies and eventually to the semi-perfluoroalkyl chain.
研究领域:
生物化学
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材料科学
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分子生物学
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产品关联
DOI
高影响因子
EXPERIMENTAL DERMATOLOGY
·
2019
·Vol. 28
·期 11
·1227-1236
·
IF 2.868
Fei Yi,Xiaoli Zheng,Fang Fang,Jiaan Zhang,Bingrong Zhou,Xiangsheng Chen
Background Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is a well-known treatment for non-hypertrophic actinic keratoses and superficial basal-cell carcinomas. Objectives In this study, we first revealed that ALA-PDT treatment effectively ameliorated the psoriasis-like lesion in imiquimod (IMQ)-induced mouse model and further explored the potential molecular mechanism and related signalling pathways during the treatment. Besides, we also confirmed a significant alleviation of ALA-PDT therapy on IFN-γ-induced over-proliferation of keratinocytes. Methods H&E staining was conducted to reveal the histological changes of mice in different groups. The different expression levels of RNA were illustrated by using QRT-PCR. Western blot was performed to confirm the various expression levels of protein in mice. In vitro, cell proliferation and cell cycle were evaluated by cell counting kit-8 and flow cytometry assay, respectively. Results The result showed that ALA-PDT’s anti-proliferation effect and regulation on Socs1 /3, JAK1 /2 and K17 in IFN-γ-induced keratinocytes were largely weakened by NAC, indicating that ALA-PDT attenuated the proliferation of IFN-γ-induced keratinocytes by enhancing ROS level. Conclusions These results demonstrated that ALA-PDT largely activated the productivity of Socs1 /3 in a ROS-dependent manner. Socs1 /3 is a potential blocker in JAK signalling pathway and inhibits the proliferation and keratinization of keratinocytes in psoriasis.
研究领域:
皮肤科
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分子生物学
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光动力疗法
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DOI
PubMed
高影响因子
TRANSACTIONS OF TIANJIN UNIVERSITY
·
2018
·Vol. 24
·期 6
·513-521
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IF 0
Shan Yuyao,Qi Wei,Wang Mengfan,Su Rongxin,He Zhimin
Recently, enzymatic peptide synthesis has drawn increasing attention due to its eco-friendly reagents and mild conditions, as compared to traditional chemical peptide synthesis. In this study, we successfully produced an important antioxidant dipeptide precursor, BOC-Tyr-Ala, via a kinetically controlled enzymatic peptide synthesis reaction, catalyzed by the recombinant carboxypeptidase Y (CPY) expressed in P. pastoris GS115. In this reaction, the enzyme activity was 95.043 U/mL, and we used t -butyloxycarbonyl- l -tyrosine-methyl ester (BOC-Tyr-OMe) as the acyl donor and l -alanine ( l -Ala) was the amino donor. We optimized the reaction conditions to be: 30 °C, pH 9.5, organic phase (methanol)/aqueous phase = 1:20, BOC-Tyr-OMe 0.05 mol/L, Ala 0.5 mol/L, and a reaction time of 12 h. Under these conditions, the dipeptide yield reached 49.84%. Then, we established the kinetic model of the synthesis reaction in the form of Michaelis–Menten equation according to the concentration–time curve during the process and the transpeptidation mechanism. We calculated the apparent Michaelis constant \(K_{\text{m}}^{\text{app}}\) and the apparent maximum reaction rate \(r_{\hbox{max} }^{\text{app}}\) to be \(2.9946 \times 10^{{^{ - 2} }} {\text{ mol/L}}\) and \(2.0406 \times 10^{ - 2} {\text{ mmol/(mL}}\,{\text{h)}}\) , respectively.
研究领域:
生物技术
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酶学
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肽化学
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产品关联
DOI
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Ying Wen,Zhen Zou,Yitong Li,Danhua Zhang,Ziru Liu,Hong Liu,Xiejia Li,Wei Wu,Liyun Zeng,Qiongyan Zou,Wenjun Yi
The combination of photodynamic therapy (PDT) and gene therapy is a viable therapeutic approach for the management of secondary hyperparathyroidism (SHPT). Nevertheless, the effective delivery of photosensitizers or nucleotide drugs remains a crucial limitation in achieving therapeutic efficacy. MiR-146b-3p directly targeted BCL2, and its overexpression enhanced the antiproliferative, proautophagic, and proapoptotic effects during 5-aminolevulinic acid (5-ALA)-mediated PDT in this study. Herein, we investigated the potential of codelivering 5-ALA and miR-146b-3p to SHPT primary cells via polyamidoamine (PAMAM) and achieving enhanced therapeutic efficacy relative to that of monotreatment. The fabrication of the PAMAM-based 5-ALA and miR-146b-3p dual-delivery system (5-ALA@PAMAM/miR) involved the use of covalent condensation reactions and electrostatic self-assembly. The nanoparticles were characterized by various analytical techniques, including transmission electron microscopy (TEM), zeta potential measurements, and size measurements. Fluorescence and confocal laser scanning microscopy demonstrated a greater degree of cellular uptake of nanoparticles. Moreover, the synthesized nanoparticles considerably enhanced the effectiveness of PDT without systemic toxicity both in vitro and in vivo. Overall, the nanocarrier-gene-photosensitizer coloaded system is a promising platform for the efficient simultaneous delivery of miR-146b-3p and 5-ALA and achieves synergistic therapeutic effects.
研究领域:
医学
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药学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Small
·
2015
·Vol. 11
·期 47
·6338-6346
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IF 8.368
Jing Tan,Chuanyu Sun,Ke Xu,Changchun Wang,Jia Guo
5-Aminolevulinic acid (ALA) is a widely used photodynamic therapy (PDT) prodrug in the clinic. It can be metalized to the photosensitizer PpIX, which produces toxic singlet oxygen to kill cancer cells upon visible light irradiation. Herein, a core/shell-structured vehicle is designed to comprise magnetite colloidal supraparticles (MCSPs) as cores and ALA-Zn II coordination polymers as shells (Fe 3 O 4 @ALA-Zn II ) for target pro-photosensitizer delivery. The coordination polymers with 2D layered structures are locally deposited on the MCSPs by the complexation of the ALA and Zn II ions, and are readily controlled by varying the feed precursors and reaction temperatures. The maximum conjugated ALA amount is up to 17%. The Fe 3 O 4 @ALA-Zn II microspheres exhibit pH-sensitive release of ALA in acidic environment and rapid magnetic responsiveness. Cytotoxicity results demonstrate that Fe 3 O 4 @ALA-Zn II shows a significant inhibitory effect to T24 cells and is nontoxic to 293T normal cells as exposed to the 630 nm visible light for a very short time, which may due to the selective accumulation of ALA-induced PpIX in T24 cancer cells. Compared to the ALA used alone, the coordination polymer form is more efficient because of the bioactivity of incorporated Zn ions despite underlying the same apoptosis mechanism as ALA agent.
研究领域:
材料科学
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纳米技术
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药学
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Qiqi Yin,Yanli Yao,Handan Zhang,Jie Zhang,Jiaming Gao,Lin Weng,Tao Liu,Shuyang Sun,Xin Chen
The management of oral squamous cell carcinoma (OSCC) poses significant challenges, leading to organ impairment and ineffective treatment of deep-seated tumors, adversely affecting patient prognosis. We introduced a cascade nanoreactor that integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT) for comprehensive multimodal OSCC treatment. Utilizing iron oxide nanoparticles and mesoporous silica, we developed the FMMSH drug delivery system, encapsulating the photosensitizer prodrug δ-aminolevulinic acid (δ-ALA). Triphenylphosphine (TPP) modification facilitated mitochondrial targeting, while tumor cell membrane (TCM) coating provided homotypic targeting. The dual-targeting δ-ALA@FMMSH-TPP-TCM nanoparticles demonstrated efficacy in eradicating both superficial and deep tumors through synergistic PDT/CDT. Esterase overexpression in OSCC cells triggered δ-ALA release, and excessive hydrogen peroxide in tumor mitochondria underwent Fenton chemistry for CDT. The synergistic interaction of PDT and CDT mechanisms increased cytotoxic ROS levels, intensifying oxidative stress and enhancing apoptotic and damage mechanisms, ultimately leading to enhanced tumor cell death. PDT/CDT-induced apoptosis generated δ-ALA-containing apoptotic bodies, enhancing anti-tumor efficacy in deep tumor cells. The advantageous anatomical accessibility of oral cancer emphasizes the potential of intratumoral injection for precise and localized treatment delivery, ensuring focused therapeutic agent delivery to maximize efficacy while minimizing systemic side effects. Thus, δ-ALA@FMMSH-TPP-TCM, tailored for intratumoral injection, emerges as a transformative modality in OSCC treatment. This article is protected by copyright. All rights reserved
研究领域:
纳米技术
·
肿瘤学
·
治疗学
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2024
·
IF 4.3
Qian Zhou,Dankui Liao,Haibo Liu,Lei Wang,Xueping Zhang,Lixia Sun,Zhangfa Tong,Xuezhen Feng,Guangzhi Zhou
Food-derived angiotensin-converting enzyme inhibitory peptide (ACEIP) has an effect in supportive therapeutic on hypertension. Bovine serum albumin (BSA) as a model transporter protein to explore the interaction mechanisms with casein-hydrolyzed ACEIP Val-Ala-Pro (VAP) by multi-spectroscopic, biolayer interferometry (BLI), isothermal titration calorimetry (ITC), molecular docking, and molecular dynamics simulations. Multi-spectroscopic analysis showed that the non-covalent complexes formed by VAP and BSA resulted in decreased hydrophobicity and α-helix contents on BSA, revealing the unfolding of the BSA structure. BLI revealed the reversible binding process of BSA to VAP. ITC confirmed that the combination of VAP to BSA was a spontaneous process mainly driven by entropy. Molecular docking and molecular dynamic simulations showed that VAP was primarily bound in site II of BSA by hydrogen bonding, hydrophobic interactions, van der Waals force, and electrostatic force. This study provides a systematic method to reveal the structure–activity relationship of ACEIPs.
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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生物物理学
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产品关联
DOI
PubMed
高影响因子
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
·
2022
·Vol. 261
·期 3
·735-748
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IF 3.535
Li Zhen,Han Yu,Ji Yan,Sun Kexin,Chen Yanyi,Hu Ke
Purpose Oxidative stress and inflammation had been proved to play important role in the progression of diabetic keratopathy (DK). The excessive accumulation of AGEs and their bond to AGE receptor (RAGE) in corneas that cause the formation of oxygen radicals and the release of inflammatory cytokines, induce cell apoptosis. Our current study was aimed to evaluate the effect of ALA on AGEs accumulation as well as to study the molecular mechanism of ALA against AGE-RAGE axis mediated oxidative stress, apoptosis, and inflammation in HG-induced HCECs, so as to provide cytological basis for the treatment of DK. Methods HCECs were cultured in a variety concentration of glucose medium (5.5, 10, 25, 30, 40, and 50 mM) for 48 h. The cell proliferation was evaluated by CCK-8 assay. Apoptosis was investigated with the Annexin V- fluorescein isothiocyanate (V-FITC)/PI kit, while, the apoptotic cells were determined by flow cytometer and TUNEL cells apoptosis Kit. According to the results of cell proliferation and cell apoptosis, 25 mM glucose medium was used in the following HG experiment. The effect of ALA on HG-induced HCECs was evaluated. The HCECs were treated with 5.5 mM glucose (normal glucose group, NG group), 5.5 mM glucose + 22.5 mM mannitol (osmotic pressure control group, OP group), 25 mM glucose (high glucose group, HG group) and 25 mM glucose + ALA (HG + ALA group) for 24 and 48 h. The accumulation of intracellular AGEs was detected by ELISA kit. The RAGE, catalase (CAT), superoxide dismutase 2 (SOD2), cleaved cysteine-aspartic acid protease-3 (Cleaved caspase-3), Toll-like receptors 4 (TLR4), Nod-like receptor protein 3 (NLRP3) inflammasome, interleukin 1 beta (IL-1 ß), and interleukin 18 (IL-18) were quantified by RT-PCR, Western blotting, and Immunofluorescence, respectively. Reactive oxygen species (ROS) production was evaluated by fluorescence microscope and fluorescence microplate reader. Results When the glucose medium was higher than 25 mM, cell proliferation was significantly inhibited and apoptosis ratio was increased ( P < 0.001). In HG environment, ALA treatment alleviated the inhibition of HCECs in a dose-dependent manner, 25 μM ALA was the minimum effective dose. ALA could significantly reduce the intracellular accumulation of AGEs ( P < 0.001), activate protein and genes expression of CAT and SOD2 ( P < 0.001), and therefore inhibited ROS-induced oxidative stress and cells apoptosis. Besides, ALA could effectively down-regulate the protein and gene level of RAGE, TLR4, NLRP3, IL-1B, IL-18 ( P < 0.05), and therefore alleviated AGEs-RAGE-TLR4-NLRP3 pathway–induced inflammation in HG-induced HCECs. Conclusion Our study indicated that ALA could be a desired treatment for DK due to its potential capacity of reducing accumulation of advanced glycation end products (AGEs) and down-regulating AGE-RAGE axis–mediated oxidative stress, cell apoptosis, and inflammation in high glucose (HG)–induced human corneal epithelial cells (HCECs), which may provide cytological basis for therapeutic targets that are ultimately of clinical benefit.
研究领域:
眼科学
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细胞生物学
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分子生物学
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糖尿病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Meng Dong,Feng Liang,Shuang Cui,Bing-Bing Mao,Xu-Hui Huang,Lei Qin
The effect of steaming treatment on salmon quality was explored by different multi-omics and electronic sensory system in this study. A comparison between conventional steaming (CS) and anaerobic steaming (AS) was conducted in organoleptic quality of salmon. Twelve key volatile compounds were identified, which contributed to the flavor difference. The concentrations of hexanal, (E)-2-octen-1-al, and decanal in AS salmon were significantly lower than in CS salmon, which account for 68.9–80.5 % of the latter. During steaming, the fatty acids and diacylglycerols decreased significantly by 37.4 % and 57.9 %, respectively. Anaerobic steaming limited the degradation of some oxidized lipids, further reduced some volatile secondary oxidation products. Nucleotides and derivatives, succinic acid, glutamic acid, hydroxyproline and betaine contributed to the saltness, umami, richness of steamed salmon. Metabolomics data revealed that the higher creatinine, Ala-Ala and Ala-Leu provided more umami and less bitterness to AS salmon.
研究领域:
食品科学
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生物化学
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感官科学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 28
·12585-12592
·
IF 3.591
Shuwei Lin,Qiyun Tong,Pan Jiang,Baozong Li,Yi Li,Yonggang Yang
Three dipeptides based on the Ala–Ala building block with different substituent positions of the dodecyloxy group on the benzoyl residue at the N terminus were designed and synthesized (ortho-, meta- and para-16). All of them were able to spontaneously self-assemble in the mixed solvent of methanol and water (6/4, v/v). However, three dipeptides underwent a distinct kinetically controlled self-assembling process. The spectroscopic study also revealed that, for ortho-16, the phenylene groups and the peptide sequence loosely packed, while meta- and para-16 stacked into well-ordered structures with the formation of parallel β-sheets through supramolecular self-assembly. Intramolecular hydrogen bonding and steric hindrance of the dodecyloxy side chain were proposed to lead to the different self-assembling behaviour of the three isomers.
研究领域:
生物化学
·
超分子化学
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产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2019
·
IF 5.122
Pan Xuewei,Sun Changhao,Tang Mi,Liu Chao,Zhang Jianing,You Jiajia,Osire Tolbert,Sun Yang,Zhao Youxi,Xu Meijuan,Yang Taowei,Rao Zhiming
Serratia marcescens, a gram-negative bacterium, found in a wide range of ecological niches can produce several high-value products, including prodigiosin, althiomycin, and serratamolide. Among them, prodigiosin has attracted attention due to its immunosuppressive, antimicrobial, and anticancer properties. However, the regulatory mechanisms behind prodigiosin synthesis in Serratia marcescens remains limited. Here, a transposon mutant library was constructed to identify the genes related to prodigiosin synthesis, and BVG90_02415 gene encoding a peptidoglycan synthesizing enzyme D-Ala-D-Ala carboxypeptidase DacA was found to negatively regulates prodigiosin synthesis. Quantitative measurements revealed that disruption of dacA increased prodigiosin production 1.46-fold that of the wild-type strain JNB5-1 in fermentation medium. By comparing differences in cell growth, pigA gene expression level, cell morphology, membrane permeability, and intracellular prodigiosin concentration between wild-type strain JNB5-1 and dacA mutant SK4-72, results revealed that the mechanism for hyper-producing of prodigiosin by the dacA mutant was probably that dacA disruption enhanced prodigiosin leakage, which in turn alleviated feedback inhibition of prodigiosin and increased expression of pig gene cluster. Collectively, this work provides a novel insight into regulatory mechanisms of prodigiosin synthesis and uncovers new roles of DacA protein in regulating cell growth, cell morphology, and membrane permeability in Serratia marcescens. Finally, this study offers a new strategy for improving production of high-value compounds in Serratia marcescens.
研究领域:
微生物学
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生物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2022
·
IF 6.064
Zhu Huajie,Xu Cuihong,Chen Yicun,Liang Yan
Burkholderia arboris, which belongs to the Burkholderia cepacia complex, has been shown to possess antifungal activity against several plant fungal pathogens; however, the antifungal compounds are yet to be identified. Here, we identified the antifungal compounds produced by B. arboris using genetic and metabolomic approaches. We generated a Tn5 transposon mutation library of 3,000 B. arboris mutants and isolated three mutants with reduced antifungal activity against the plant fungal pathogen Fusarium oxysporum. Among the mutants, the M464 mutant exhibited the weakest antifungal activity. In the M464 genome, the transposon was inserted into the cobA gene, encoding uroporphyrin-III methyltransferase. Deletion of the cobA gene also resulted in reduced antifungal activity, indicating that the cobA gene contributed to the antifungal activity of B. arboris. Furthermore, a comparison of the differential metabolites between wild type B. arboris and the ∆cobA mutant showed a significantly decreased level of tetrapeptide His-Ala-Phe-Lys (Hafk) in the ∆cobA mutant. Therefore, a Hafk peptide with D-amino acid residues was synthesized and its antifungal activity was evaluated. Notably, the Hafk peptide displayed significant antifungal activity against F. oxysporum and Botrytis cinerea, two plant pathogens that cause destructive fungal diseases. Overall, a novel antifungal compound (Hafk) that can be used for the biocontrol of fungal diseases in plants was identified in B. arboris.
研究领域:
微生物学
·
植物病理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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