ChemBioChem最新文献_第10页

(+)-3,6-Epoxymaaliane: A Novel Derivative of (+)-Bicyclogermacrene Oxidation Catalyzed by CYP450 BM3-139-3 and Its Variants (+)-3,6-环氧马来酰亚胺：一种由 CYP450 BM3-139-3 及其变体催化的 (+)-Bicyclogermacrene 氧化作用的新型衍生物。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-27 DOI: 10.1002/cbic.202400410

Kai Xu, Zheng-Yu Huang, Chen-Yi Sun, Dr. Jiang Pan, Prof. Dr. Chun-Xiu Li, Prof. Dr. Jian-He Xu

{"title":"(+)-3,6-Epoxymaaliane: A Novel Derivative of (+)-Bicyclogermacrene Oxidation Catalyzed by CYP450 BM3-139-3 and Its Variants","authors":"Kai Xu, Zheng-Yu Huang, Chen-Yi Sun, Dr. Jiang Pan, Prof. Dr. Chun-Xiu Li, Prof. Dr. Jian-He Xu","doi":"10.1002/cbic.202400410","DOIUrl":"10.1002/cbic.202400410","url":null,"abstract":"(+)-Bicyclogermacrene is a sesquiterpene compound found in various plant essential oils and serves as a crucial precursor for multiple biologically active compounds. Many derivatives of (+)-bicyclogermacrene have been shown to exhibit valuable bioactivities. Cytochrome P450 BM3 from Bacillus megaterium can catalyze a variety of substrates and different types of oxidation reactions, making it become a powerful tool for oxidizing terpenes. In this study, we employed P450 BM3-139-3 variant for in vitro enzymatic oxidation of (+)-bicyclogermacrene, identifying a novel oxidized derivative of (+)-bicyclogermacrene, named (+)-3,6-epoxymaaliane, and an unknown sesquiterpenoid in a ratio of 70 : 30 (by GC peak area). (+)-3,6-Epoxymaaliane showed demonstrated antibacterial activities toward Escherichia coli and Staphylococcus aureus. To obtain a better variant of the monooxygenase with a high selectivity to form (+)-3,6-epoxymaaliane, we combined alanine scanning with the “Focused Rational Iterative Site-Specific Mutagenesis” (FRISM) strategy to modify the closest residues within 5 Å radius surrounding the substrate to create a small-but-smart library of mutants. Consequently, it gave an optimal variant with 1.6-fold improvement, in a turnover number (TON) of up to 964 toward (+)-3,6-epoxymaaliane production with a higher product selectivity.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"25 22","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ferrocenyl β-Diketonate Compounds: Extended Ring Systems for Improved Anticancer Activity. 二茂铁基 β-二酮化合物：用于提高抗癌活性的扩展环系统。

IF 4.6 4区生物学

ChemBioChem Pub Date : 2024-10-24 DOI: 10.1002/cbic.202400759

Benjamin J Hofmann, Enas T Aljohani, Natalia Cicovacki, Ivan Lee, Derek T Warren, Anastasia Sobolewski, Tameryn Stringer, Rianne M Lord

{"title":"Ferrocenyl β-Diketonate Compounds: Extended Ring Systems for Improved Anticancer Activity.","authors":"Benjamin J Hofmann, Enas T Aljohani, Natalia Cicovacki, Ivan Lee, Derek T Warren, Anastasia Sobolewski, Tameryn Stringer, Rianne M Lord","doi":"10.1002/cbic.202400759","DOIUrl":"10.1002/cbic.202400759","url":null,"abstract":"A library of ferrocenyl β-diketonate compounds with varying degrees of aromatic functionality have been synthesized and fully characterized. This includes cyclic voltammetry and the analysis of four new structures by single crystal X-ray diffraction. The compounds cytotoxic potential has been determined by MTT screening against pancreatic carcinoma (MIA PaCa-2), ovarian adenocarcinoma (A2780), breast adenocarcinomas (MDA-MB-231 and MCF-7) and normal epithelial retinal (ARPE-19). The compounds show a general trend, where increasing the number of aromatic rings in the molecule yields an increase in cytotoxicity and follows the trend anthracenyl>naphthyl>phenyl>methyl. The compounds are particularly sensitive to the triple negative cancer cell line MDA-MB-231, and the potential modes of action have been studied by production of reactive oxygen species using fluorescence microscopy and cell morphology using Scanning Electron Microscopy. All assays highlight the ferrocenyl β-diketonate with an anthracenyl substituent to be the lead compound in this library. The decomposition of this compound was also observed within cells, yielding a cytotoxic fluorescent molecule, which has been visualized by confocal microscopy.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400759"},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Light-driven Lytic Polysaccharide Monooxygenase Catalysis Mediated by Type I Photosensitizers 由 I 型光敏剂介导的光驱动溶解多糖单氧化酶催化。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-24 DOI: 10.1002/cbic.202400486

Ana Gabriela Veiga Sepulchro, Milena Moreira Vacilotto, Lucas D. Dias, Vanessa O. A. Pellegrini, Josman Velasco., Natalia M. Inada, Fernando Segato, Igor Polikarpov

{"title":"Light-driven Lytic Polysaccharide Monooxygenase Catalysis Mediated by Type I Photosensitizers","authors":"Ana Gabriela Veiga Sepulchro, Milena Moreira Vacilotto, Lucas D. Dias, Vanessa O. A. Pellegrini, Josman Velasco., Natalia M. Inada, Fernando Segato, Igor Polikarpov","doi":"10.1002/cbic.202400486","DOIUrl":"10.1002/cbic.202400486","url":null,"abstract":"The use of light as abundant, renewable, and clean energy source to boost lytic polysaccharide monooxygenase (LPMO) reactions represents an exciting and yet under-explored opportunity. Herein we demonstrated that photosensitizers, commonly used in photodynamic therapy, which act through the photocatalytic Type I mechanism can drive the oxidation of PASC by LPMOs, whereas Type II photosensitizers are not capable of promoting the LPMO activity. We analyzed Type I and Type II photosensitizers (methylene blue and tetraiodide salt of meso-tetrakis-(4-N-methylpyridyl) porphyrin, respectively) and demonstrated that, even without an addition of external reductant, Type I was capable of boosting Thermothelomyces thermophila MtLPMO9A activity in the presence of light. We also evaluated the photobiosystem in the presence and/or absence of molecular oxygen (O2) and hydrogen peroxide (H2O2), and investigated the role of superoxide radical in the methylene blue fueled reactions. Furthermore, we demonstrated that sodium bisulfite (NaHSO3), a chemical scavenger of H2O2, acts by safeguarding the enzyme from oxidative damage caused by accumulation of H2O2 early in photosensitizer-driven LPMO reactions. Finally, the results of the present work demonstrated that light-driven LPMO reactions mediated photodynamic therapy (PDT) Type I photosensitizers, which also includes molecules such as curcumin and riboflavin, is a general phenomenon.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"25 23","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implications of the Lipidic Ecosystem for the Membrane Binding of ApoE Signal Peptide: Importance of Sphingomyelin 脂质生态系统对载脂蛋白信号肽膜结合的影响：鞘磷脂的重要性

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-23 DOI: 10.1002/cbic.202400469

Sasmita Pradhan, Lipika Mirdha, Tanusree Sengupta, Hirak Chakraborty

{"title":"Implications of the Lipidic Ecosystem for the Membrane Binding of ApoE Signal Peptide: Importance of Sphingomyelin","authors":"Sasmita Pradhan, Lipika Mirdha, Tanusree Sengupta, Hirak Chakraborty","doi":"10.1002/cbic.202400469","DOIUrl":"10.1002/cbic.202400469","url":null,"abstract":"The unidirectional movement of nascent secretory proteins in the cell is primarily assisted by the signal recognition particles (SRP). However, this does not completely justify the importance of the signal peptide (SP) which gets eliminated after the protein translocation. We have earlier demonstrated that a negatively charged lipid such as POPG plays an important role in the higher binding affinity and cholesterol-discriminating ability of the apolipoprotein E (ApoE) SP. In this present work, we aimed to understand the role of sphingomyelin, an important constituent of ER, on the membrane binding of ApoE SP. Our results demonstrate that sphingomyelin promotes membrane binding but cannot discriminate cholesterol. However, sphingomyelin shows a synergistic effect with POPG toward the membrane binding of the ApoE SP. We have further shown that the membrane domains do not have any impact on the binding of ApoE SP. Based on our results we propose that the lipid composition of the endoplasmic reticulum (ER) where ApoE translocates, enhances the binding of the ApoE signal peptide to the ER membrane.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"25 22","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Detection Strategies for Sialic Acid and Sialoglycoconjugates 唾液酸和唾液酸共轭物的检测策略

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-23 DOI: 10.1002/cbic.202400402

Carmanah D. Hunter, Christopher W. Cairo

{"title":"Detection Strategies for Sialic Acid and Sialoglycoconjugates","authors":"Carmanah D. Hunter, Christopher W. Cairo","doi":"10.1002/cbic.202400402","DOIUrl":"10.1002/cbic.202400402","url":null,"abstract":"Glycoconjugates are a vast class of biomolecules implicated in biological processes important for human health and disease. The structural complexity of glycoconjugates remains a challenge to deciphering their precise biological roles and for their development as biomarkers and therapeutics. Human glycoconjugates on the outside of the cell are modified with sialic (neuraminic) acid residues at their termini. The enzymes that install sialic acids are sialyltransferases (SiaTs), a family of 20 different isoenzymes. The removal and degradation of sialic acids is mediated by neuraminidase (NEU; sialidase) enzymes, of which there are four isoenzymes. In this review, we discuss chemical and biochemical approaches for the detection and analysis of sialoglycoconjugate (SGC) structures and their enzymatic products. The most common methods include affinity probes and synthetic substrates. Fluorogenic and radiolabelled substrates are also important tools for many applications, including screening for enzyme inhibitors. Strategies that give insight into the native substrate-specificity of enzymes that regulate SGCs (SiaT & NEU) are necessary to improve our understanding of the role of sialic acid metabolism in health and disease.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"25 23","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202400402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Precursor-Directed Biosynthesis of Panepoxydone Derivatives with Nitric Oxide Production Inhibitory Activity. 具有一氧化氮生成抑制活性的 Panepoxydone 衍生物的前体定向生物合成。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-22 DOI: 10.1002/cbic.202400691

Huiping Yu, Xuejing Hao, Yungeng Gao, Lin Yang, Yao Qin, Xiaoqing Li, Yan-Long Yang

引用次数: 0

Nanozymes as Antibacterial Agents: New Concerns in Design and Enhancement Strategies. 纳米酶作为抗菌剂：设计和增强策略的新关注点。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-21 DOI: 10.1002/cbic.202400677

Xianhang Yan, Xiaoqiang Li, Pengtian Yu, Lijun Wang, Qingwei Zhao

{"title":"Nanozymes as Antibacterial Agents: New Concerns in Design and Enhancement Strategies.","authors":"Xianhang Yan, Xiaoqiang Li, Pengtian Yu, Lijun Wang, Qingwei Zhao","doi":"10.1002/cbic.202400677","DOIUrl":"10.1002/cbic.202400677","url":null,"abstract":"Nanozymes exhibiting natural enzyme-mimicking catalytic activities as antibacterial agents present several advantages, including high stability, low cost, broad-spectrum antibacterial activity, ease of preparation and storage, and minimal bacterial resistance. Consequently, they have attracted significant attention in recent years. However, the rapid expansion of antimicrobial nanozyme research has resulted in pioneering reviews that do not comprehensively address emerging concerns and enhancement strategies within this field. This paper first summarizes the factors influencing the intrinsic activity of nanozymes; subsequently, we outline new research considerations for designing antibacterial nanozymes with enhanced functionality and biosafety features such as degradable, imageable, targeted, and bacterial-binding nanozymes as well as those capable of selectively targeting pathogenic bacteria while sparing normal cells and probiotics. Furthermore, we review novel enhancement strategies involving external physical stimuli (light or ultrasound), the introduction of extrinsic small molecules, and self-supplying H2O2 to enhance the activity of antibacterial nanozymes under physiological conditions characterized by low concentrations of H2O2 and O2. Additionally, we present non-redox nanozymes that operate independently of highly toxic reactive oxygen species (ROS) alongside those designed to combat less common pathogenic bacteria. Finally, we discuss current issues, challenges faced in the field, and future prospects for antibacterial nanozymes.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400677"},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic Nanostructure-Based DNA Logic Gates for Cancer Diagnosis and Therapy. 用于癌症诊断和治疗的动态纳米结构 DNA 逻辑门。

IF 4.6 4区生物学

ChemBioChem Pub Date : 2024-10-21 DOI: 10.1002/cbic.202400754

Shiyi Bi, Ruowen Yang, Huangxian Ju, Ying Liu

引用次数: 0

Noncanonical Functions of Ketosynthase Domains in Type I Polyketide Synthases. I 型多酮合成酶中酮合成酶结构域的非规范功能

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-21 DOI: 10.1002/cbic.202400751

Yuqiong Zhao, Wenyu Zhang, Wen Liu, Zhijun Tang

引用次数: 0

Binding Mode of Cyclic Chemerin-9 Peptide and ChemerinS157 Protein at CMKLR1. 环状螯合素-9 肽和螯合素-S157 蛋白在 CMKLR 上的结合模式。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-18 DOI: 10.1002/cbic.202400695

Tina Schermeng, Fabian Liessmann, Carla Katharina Ambrosius, Jens Meiler, Annette G Beck-Sickinger

{"title":"Binding Mode of Cyclic Chemerin-9 Peptide and ChemerinS157 Protein at CMKLR1.","authors":"Tina Schermeng, Fabian Liessmann, Carla Katharina Ambrosius, Jens Meiler, Annette G Beck-Sickinger","doi":"10.1002/cbic.202400695","DOIUrl":"10.1002/cbic.202400695","url":null,"abstract":"The chemokine-like receptor 1 (CMKLR1) is activated by the adipokine and chemoattractant protein chemerin. Cryo-EM structures of chemerin-9-CMKLR1-Gi have been published, where chemerin-9 is the nonapeptide of the C terminus of chemerinS157. Chemerin-9 is as active as the full-length protein in Ca2+-release but shows differences in equilibrium read-outs. An equally potent cyclic chemerin-9 variant (cC9) was reported previously. Now, we have built a computational model of CMKLR1 to investigate the binding mode of cC9 and chemerinS157 in comparison to chemerin-9. Differences were investigated using CMKLR1 variants. Double-mutant cycle analysis identified CMKLR1-F2.53 as the relevant position for Phe8-binding of cC9. Energy contribution revealed slight differences in Phe8-binding to CMKLR1-F2.53 and space for larger residues. This was confirmed as the chemerin-9 variant with 1-naphthyl-L-alanine at position 8 showed a 4-fold increased potency of 2 nM (pEC50=8.6±0.15). While chemerin-9 and cC9 share their interactions at the CMKLR1, chemerinS157 tolerates most mutations of CMKLR1 in the deep binding site. The computational model of chemerinS157 suggests a β-sheet interaction between the N-terminal CMKLR1-segment I25VVL28 and the β-sheet D108KVLGRLVH116 of ChemS157, which was confirmed experimentally. Our data add to the knowledge by identifying the binding mode of chemerinS157 and cC9 at CMKLR1, facilitating the future structure-based drug design.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400695"},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0