FOOD CONTROL
·
2022
·
IF 6.652
Zhiyong Zhao,Hengchao E,Enjing Tian,Tingting Fan,Xianli Yang,Xiaobei Li,Yanmei Zhang,Xujiao Li,Ailiang Chen,Changyan Zhou,Xiaoyan Zhao
Foodborne poisoning caused by the cyclopeptide toxins-producing mushroom species seriously endangers human life health. In recent years discovery of new cyclopeptides is getting more attention not only for their toxicity but also for their specific bioactivity. In this study, a combined strategy using liquid chromatography tandem high resolution mass spectrometry and the feature-based molecular networking analysis was established to identify the known cyclopeptide toxins and discover new cyclopeptides in the cyclopeptide toxins-producing mushroom species. The specific fragmentation behaviors of the known cyclopeptide toxins were systematically annotated. Four new phallotoxin analogues were identified for the first time, the chemical structures of which were completely deduced. Moreover, the chemical profiles of the toxic cyclopeptides in lethal mushroom Amanita and Lepiota species were investigated by the self-built cyclopeptides database. The developed strategy could be utilized as a useful tool for identifying the cyclopeptide toxins-induced food poisoning , as well as aid in the discovery of more unknown cyclopeptides.
研究领域:
食品科学
·
毒理学
·
分析化学
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DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Yahong Tan,Jinyue Yang,Min Wang,Qi Peng,Yongqi Li,Lifeng Fu,Mengmeng Zhang,Jiang Wu,Guanya Yang,Christopher John Hipolito,Youming Zhang,Jianxun Qi,Yi Shi,Yizhen Yin
Macrocyclic peptides have garnered significant attention as promising drug candidates. However, they typically face challenges in achieving and enhancing cell permeability for access to intracellular targets. In this study, we focused on the de novo screening of macrocyclic peptide inhibitors against the main protease (Mpro) of SARS-CoV-2 and identified novel noncovalently bound macrocyclic peptides that effectively inhibit proteolytic activity. High-resolution crystal structures further revealed molecular interactions between the macrocyclic peptides and Mpro. Subsequently, a specific macrocyclic peptide lacking cell permeability was further optimized and transformed into a low-toxicity, metabolically stable bicyclic peptide with a cell penetration capacity and therapeutic potential against SARS-CoV-2. The bicyclic peptide was achieved using a novel strategy that involved introducing both a bicyclic structure and a bridging perfluorobiphenyl group. Our study not only provides a lead peptide inhibitor for COVID-19 but also offers valuable insights into achieving cell penetration for macrocyclic peptides through strategic modifications.
研究领域:
药理学
·
病毒学
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药物发现
·
蛋白质工程
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DOI
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2025
·Vol. 122
·期 13
·e2426006122
·
IF 9.1
Fengwei Li,Mengmeng Zhang,Chao Liu,Jie Cheng,Yawen Yang,Xiangda Peng,Zhifeng Li,Wenfeng Cai,Haipeng Yu,Junjie Wu,Yuyu Guo,Hongkun Geng,Yun Fa,Youming Zhang,Dalei Wu,Yizhen Yin
Macrocyclic peptides have emerged as promising drug candidates, filling the gap between small molecules and large biomolecules in drug discovery. The antiapoptotic protein myeloid cell leukemia 1 (MCL1) is crucial for numerous cancers, yet it presents challenges for selective targeting by traditional inhibitors. In this study, we identified a macrocyclic peptide, 5L1, that strongly binds to MCL1, with a dissociation constant (KD) of 7.1 nM. This peptide shows the potential to specifically inhibit the function of MCL1, and demonstrates effective antitumor activity against several blood tumor cell lines with the half maximal inhibitory concentration (IC50) values for cell-penetrating peptide-conjugated 5L1 in the range of 0.6 to 3 μM. Structural analysis revealed that it functions similarly to molecular glue, capable of binding to two MCL1 molecules simultaneously and inducing their homodimerization. This unique mechanism of action distinguishes it from traditional small-molecule MCL1 inhibitors, underscoring the potential of macrocyclic peptides functioning as molecular glues. Moreover, it inspires the development of highly selective inhibitors targeting MCL1 and other related targets with this glue-like mechanism.
研究领域:
药物化学
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癌症生物学
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结构生物学
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产品关联
DOI
PubMed
高影响因子
Organic Chemistry Frontiers
·
2024
·
IF 4.6
Yueyue Xing,Tianyu Bo,Nan Zhang,Meiqi Wu,Jiawei Wang,Shigang Shen,Yafang Wang,Changying Song,Tiesheng Shi,Shuying Huo
Peptides constrained by multiple disulfide bonds (MDBs) or by thioether bridges play a critical role in improving the biological and pharmaceutical activities of peptide drugs. The synthesis of correct MDBs and thioether-bridged bicyclic peptides still remains a significant challenge. In this work, benzeneseleninic acid (BSA) acting as both an oxidant and a deprotecting reagent for the synthesis of MDB- and thioether-bridged bicyclic peptides has been investigated. Disulfide bonds in peptides can be formed by direct oxidation of two sulfhydryl groups by BSA in neutral media or via two concerted steps, namely deprotecting two acetamidomethyl (Acm) groups and oxidation by BSA in acidic media. As such, two disulfide bonds in α-conotoxin SI, apamin, α-conotoxin IMI and a peptide containing a methionine residue were synthesized regioselectively by the use of the BSA oxidation and deprotection reaction (BSA-ODr). By utilization of the BSA deprotection property, bicyclic peptides were synthesized based on the crosslinking of xylylene dibromide with sulfhydryl groups. Furthermore, two disulfide bonds in α-conotoxin SI and three disulfide bonds in conotoxin mr3e, enterotoxin STp, μ-conotoxin KIIIA, linaclotide and ziconotide were also synthesized regioselectively through oxidation of fully reduced peptides by BSA. All the reactions were carried out under mild conditions in a one-pot manner and peptides with satisfactory yields were achieved. In addition, the BSA-ODr is compatible with methionine residues in the peptides. Moreover, the relative positions of two Acm-protected cysteines and two free cysteines have no impact on the BSA-ODr approach for the construction of two disulfide bonds in peptides. The oxidative folding strategies based on BSA can be executed in peptide manufacture. BSA is readily accessible conferring efficient BSA-ODr and oxidative folding methodologies for the synthesis of MBDs and thioether bridges in peptides.
研究领域:
生物化学
·
药物化学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
·
2014
·Vol. 2014
·期 34
·7572-7576
·
IF 3.154
Lijing Fang,Chunlei Wu,Zaidan Yu,Peng Shang,Yongxian Cheng,Yuefeng Peng,Wu Su
Graphical A highly efficient protocol for the triphosgene-mediated solid-phase coupling of proteinogenic amino acids is developed and applied to the first total synthesis of the bioactive natural octacyclopeptide brachystemin A. A reproducible, highly efficient, and racemization-free protocol for the triphosgene-mediated solid-phase coupling of proteinogenic amino acids was developed. The efficiency of the reaction was demonstrated by the first total synthesis of the bioactive natural octacyclopeptide brachystemin A. This protocol will broaden the application of triphosgene in the synthesis of a wide range of peptides, including aromatic amino acids, N -alkylated amino acids, as well as proteinogenic amino acids.
研究领域:
有机化学
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药物化学
·
生物合成
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DOI
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Wentao Xu,Jiajia Zheng,Jiaqi Zhang,Houhui Shi,Weili Peng,Yang Liu,Guodong Feng,Yuguang Wang,Yi-Jun Liang,Jun Chen
Background Liver cancer is one of the most prevalent cancers globally, with approximately 90% of primary liver cancers being hepatocellular carcinomas (HCC). However, current systemic treatment options (whether monotherapy or combination therapy) are limited and offer only modest survival benefits. The effectiveness of a drug is largely determined by its concentration at the target site. Therefore, an effective drug delivery system must enhance drug accumulation at the target site, enable selective drug release there, and facilitate escape from lysosomes.Methods cRGD-Lipo@Ce6/DOX was prepared by modifying c(RGDyK) onto the surface of drug-loaded liposomes containing Chlorin e6 (Ce6) and doxorubicin (DOX) through an amide reaction. The targeting capability and uptake mechanism of cRGD-Lipo@Ce6/DOX for HCC were analyzed using flow cytometry. To investigate drug release mechanisms and changes in subcellular distribution following ultrasound stimulation, further studies were conducted. The therapeutic efficacy and biosafety of this dual-modality therapy were then evaluated in an HCC subcutaneous tumor-bearing mouse model.Results The prepared nanocomplex exhibits a surface charge of −9.91 ± 2.94 mV and an apparent size of 118.07 ± 1.46 nm. Modification of the RGD cyclic peptide on the surface of the drug-carrying liposomes enhanced the targeting and penetration efficiency for HCC. In vitro experiments on drug uptake mechanisms and release demonstrated that reactive oxygen species (ROS) generated by sonodynamic therapy (SDT) promote effective drug release from the carrier into the non-lysosomal region. The combined SDT and chemotherapy treatment achieved a 94% tumor inhibition rate and showed excellent biosafety in HCC subcutaneous tumor-bearing mice.Conclusion Therefore, the effectiveness of the combination treatment strategy utilizing SDT in conjunction with chemotherapy provides additional treatment options for patients with HCC.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
POLYMER DEGRADATION AND STABILITY
·
2020
·
IF 4.032
Xian He,Shenjun Liao,Menghao Chen,Renke Li,Yao Liu,Bo Liang,Jianghuai Hu,Ke Zeng,Gang Yang
Tyrosine derived cyclic peptide (TCP) was employed to promote the curing reaction of a phthalonitrile monomer 1,3-bis(3,4-dicyanophenoxy) (3BOCN). Differential scanning calorimetry (DSC) and rheological analysis were used to study the curing behaviors of the TCP/3BOCN blend and confirmed a relatively high curing efficiency. Fourier transform infrared spectrometer (FT-IR) and two-dimensional infrared vibrational echo spectroscopy suggested the cyclic peptide reactive site was responsible for the unique curing behavior. Isoindolin, phthalocyanine and triazine were confirmed as curing products. Thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA) were used to measure the thermal and thermomechanical properties of the cured resin. The results firstly revealed the excellent thermal stability and high glass transition temperature (T g ) of this resin even under a moderate post-curing condition.
研究领域:
材料科学
·
化学工程
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产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 5
·1-10
·
IF 5.833
Gu Ying,Hu Yuanling,Zhang Fuyuan,Yi Lunzhao,Shang Ying,Ren Dabing,Ge Zhenhua
A glucose (Glu) sensor was designed by introducing synthetic cyclic peptides (CPs) as recognition receptors and Au nanoparticles assisted graphitic carbon nitride (AuNPs/g-C 3 N 4 ) for electrochemiluminescence (ECL) enhancement. The synthetic CP receptor (cyclo-[−CNDNHCRDNDC−]) with natural active center of Glu binding protein can mimic the interactions between Glu and Glu binding protein to specifically capture Glu. The AuNPs were reduced on g-C 3 N 4 and formed a new nanohybrid that can be applied as an ECL emitter. The AuNPs/g-C 3 N 4 effectively ameliorated the ECL response of bare g-C 3 N 4 . The ECL enhancement mechanism was theoretically speculated through computer simulation. Glu quantification was conducted by recording ECL shifts induced by the binding of Glu to CPs. The linear detection range of the fabricated CPs-based ECL sensor was 1 to 100 mmol L −1 , and the detection limit (LOD) was 0.57 nmol L −1 (S / N = 3). The CP-based ECL sensor also showed good specificity, repeatability, stability, and favorable recoveries in sample analysis. This work offer a promising analytical method for Glu assay in clinical diagnostics and bioprocess monitoring. Graphical abstract
研究领域:
生物化学
·
分析化学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
POLYMER TESTING
·
2020
·
IF 3.275
Xian He,Hao Wu,Jiangbo Lv,Menghao Chen,Tao Zhou,Yun Luo,Jianghuai Hu,Ke Zeng,Gang Yang
The investigation on the curing kinetics of phthalonitrile is of significance for understanding the curing mechanism and optimizing the curing process. Here the curing kinetics of 1,3-bis (3,4-dicyanophenoxy) benzene (3BOCN) promoted by tyrosine cyclic peptide (TCP) was studied by non-isothermal differential scanning calorimetry (DSC) with the aid of two-dimensional correlation spectroscopy (2DCS). 2DCS revealed a multi-path curing reaction of 3BOCN/TCP system, so the peak fitting was used to calculate the kinetic parameters of the two curing pathways. The results showed that both curing pathways of 3BOCN/TCP system could be described by autocatalytic model, and the calculated values could fit well with the experimental data.
研究领域:
材料科学
·
化学动力学
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产品关联
DOI
高影响因子
Sensors & Diagnostics
·
2022
·Vol. 2
·期 2
·382-389
·
IF 0
Rui Han,Wenjie Hou,Yang Li,Min Chen,Caifeng Ding,Xiliang Luo
Antigen testing is an effective methodology for COVID-19 disease screening, and the receptor-binding domain of the SARS-CoV-2 spike glycoprotein (RBD) is recognized as a key biomarker for the diagnosis, treatment, and vaccination of COVID-19. However, the diagnosis of RBD directly in human biofluids remains a serious challenge owing to severe biological fouling in real samples. Herein, a sensitive electrochemical biosensor capable of detecting the RBD antigen in human blood was constructed based on a self-designed cyclic peptide. This cyclic peptide was designed to have good antifouling properties to resist nonspecific adsorption of proteins, etc. in blood, and the cyclic structure of the peptide was able to resist enzymatic hydrolysis by certain enzymes in blood, enhancing the stability of the peptide as well as the peptide-based biosensor. Compared with conventional linear peptides, the cyclic peptide possessed better antifouling properties and a much stronger anti-enzymatic hydrolysis ability. The electrochemical biosensor based on the cyclic peptide was capable of sensitively assaying RBD in the concentration range from 1.0 pg mL−1 to 100.0 ng mL−1, with a limit of detection of just 0.45 pg mL−1. Moreover, the biosensor was able to quantitatively detect RBD in real samples, and the results were more reliable than those measured with ELISA kits, especially in human blood with higher concentrations. This strategy of designing cyclic peptides for the construction of antifouling biosensors offered a new method for clinical detection of viral antigens in complex biological media like human blood.
研究领域:
生物化学
·
分析化学
·
生物医学工程
·
分子生物学
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DOI
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2022
·
IF 3.682
Heyi Mao,Yidan Zhang,Lei Wang,Anduo Zhou,Shanfeng Zhang,Jing Cao,Huang Xia
The mortality rate of cardiovascular diseases is the highest among all mortality rates worldwide. Allotransplantation and autotransplantation are limited by rejection reaction and availability. Tissue engineering provides new avenues for the treatment of cardiovascular diseases. However, the current small-diameter (<6 mm) vascular tissue-engineered scaffolds have many challenges, including thrombosis, stenosis, and infection. Small-diameter vascular scaffolds have structural and compositional requirements such as biocompatibility, porosity, and appropriate phase separation. We used liquid-crystal cyclopeptide（CYC）to modify β-cyclodextrin and mixed it with γ-glycerol methoxytrimethoxysilane (GPTMS) to prepare CYC-β-cyclodextrin (βCD)/GPTMS film by sol-gel. The chemical structure of CYC-βCD was confirmed by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance. The chemical characterization of CYC-βCD/GPTMS film was performed by differential scanning calorimetry, X-ray diffraction, and small-angle X-ray scattering. The surface morphology and phase separation microstructure of the film were determined by scanning electron microscopy and atomic force microscopy, and the image of polarizing microscopy showed the liquid-crystal structure of the film. Cell culture experiments showed that CYC-βCD/GPTMS film had good cytocompatibility and induced growth and proliferation of cells. These results indicated the potential applications of CYC-βCD/GPTMS film in tissue engineering scaffolds.
研究领域:
生物材料学
·
心血管医学
·
组织工程
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 8
·2255
·
IF 4.412
Nan Wei,Jun Zhao,Guimei Wu,Wenjuan Cao,Pei Luo,Zhifeng Zhang,Gang Chen,Lu Wen
As a consequence of recent progression in biomedicine and nanotechnology, nanoparticle-based systems have evolved as a new method with extensive applications in responsive therapy, multimodal imaging, drug delivery and natural product separation. Meanwhile, the magnetic nanoparticulate system has aroused great interest for separation and purification because of its excellent magnetic properties. Phospholipase A2(PLA2) is a highly expressed regulator to promote the growth of various cancers and is an ideal target to treat cancers. In this study, a novel strategy based on ligand–receptor interactions to discover novel PLA2inhibitors was established, in which PLA2-functionalized Fe3O4@PLGA-PEG-NH2magnetic nanoparticles were used as a supporting material combined with high-performance liquid chromatography–mass spectrometry, aiming to accelerate the discovery of novel PLA2inhibitors from natural sources such as mangrove endophytic fungi. Under the optimized ligand fishing conditions, six target compounds were ultimately fished and identified to be cyclic peptides (1–3) and sterols (4–6), which compounds1,2and4–6have well-documented cytotoxicities. Compound3exerted better inhibitory effect on A549 cells by experiment. In conclusion, PLA2-functionalized Fe3O4@PLGA-PEG-NH2magnetic nanoparticles-based ligand fishing provided a feasible, selective and effective platform for the efficient screening and identification of antitumor components from natural products.Keywords:magnetic nanoparticles;ligand fishing;phospholipase A2;endophytic fungus
研究领域:
生物医学工程
·
纳米技术
·
药理学
·
真菌学
·
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）