ChemBioChem最新文献_第5页

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":"https://doi.org/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":null,"pages":null},"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":null,"pages":null},"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 2.6 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 CMKLR. 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 CMKLR.","authors":"Tina Schermeng, Fabian Liessmann, Carla Katharina Ambrosius, Jens Meiler, Annette G Beck-Sickinger","doi":"10.1002/cbic.202400695","DOIUrl":"https://doi.org/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 expand the knowledge by identifying the binding mode of chemerinS157 and cC9 at CMKLR1 facilitating future structure-based drug design.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"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

Mechanistic Perspective on Oxygen Activation Chemistry by Flavoenzymes. 黄酮酶活化氧化学的机理透视。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-18 DOI: 10.1002/cbic.202400750

Qiaoyu Zhang, Binju Wang

引用次数: 0

A novel concept for cleavable linkers applicable to conjugation chemistry - design, synthesis and characterization. 适用于共轭化学的可裂解连接体新概念--设计、合成和表征。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-18 DOI: 10.1002/cbic.202400826

Utpal Majumder, Xiaojie Zhu, Daniel Custar, Danyang Li, Hui Fang, Sharon McGonigle, Earl Albone, Xin Cheng, Weidong Lai, Amy Siu, Karen Bresciano, Andrew Hart, Maarten Postema

{"title":"A novel concept for cleavable linkers applicable to conjugation chemistry - design, synthesis and characterization.","authors":"Utpal Majumder, Xiaojie Zhu, Daniel Custar, Danyang Li, Hui Fang, Sharon McGonigle, Earl Albone, Xin Cheng, Weidong Lai, Amy Siu, Karen Bresciano, Andrew Hart, Maarten Postema","doi":"10.1002/cbic.202400826","DOIUrl":"https://doi.org/10.1002/cbic.202400826","url":null,"abstract":"Linkers with disulfide bonds are the only cleavable linkers that utilize physiological thiol gradients as a trigger to initiate the intracellular drug release cascade. Herein, we present a novel concept exploiting the thiol gradient phenomena to design a new class of cleavable linker with no disulfide bond. To support the concept, an electron-deficient sulfonamide-based cleavable linker amenable to conjugation of drug molecules with targeting agents, was developed. Modulating the electron-withdrawing nature of the aryl sulfonamide was critical to the balance between the stability and drug release. Favorable stability and payload release in human serum under physiologically relevant thiol concentrations was demonstrated with two potent cytotoxics. Intracellular payload release was further validated in cell-based assay in context of antibody-drug conjugate generated from monoclonal antibody and sulfonamide containing linker. To support the proposed release mechanism, possible downstream by-products formed from the drug-linker adduct were characterized.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454027","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

Production of Phenyldiazene Derivatives Using the Biosynthetic Pathway of an Aromatic Diazo Group-Containing Natural Product from an Actinomycete. 利用放线菌含芳香重氮基团天然产物的生物合成途径生产苯基二氮烯衍生物。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-17 DOI: 10.1002/cbic.202400687

Seiji Kawai, Jiayu Ning, Yohei Katsuyama, Yasuo Ohnishi

{"title":"Production of Phenyldiazene Derivatives Using the Biosynthetic Pathway of an Aromatic Diazo Group-Containing Natural Product from an Actinomycete.","authors":"Seiji Kawai, Jiayu Ning, Yohei Katsuyama, Yasuo Ohnishi","doi":"10.1002/cbic.202400687","DOIUrl":"10.1002/cbic.202400687","url":null,"abstract":"The diazo group is an important functional group in organic synthesis because it confers high reactivity to the compounds and has been applied in various chemical reactions, such as the Sandmeyer reaction, Wolff rearrangement, cyclopropanation, and C-N bond formation with active methylene compounds. Previously, we revealed that 3-diazoavenalumic acid (3-DAA), which is potentially produced by several actinomycete species and contains an aromatic diazo group, is a biosynthetic intermediate of avenalumic acid. In this study, we aimed to construct a production system for phenyldiazene derivatives by adding several active methylene compounds to the culture of a 3-DAA-producing recombinant actinomycete. First, acetoacetanilide and its derivatives, which have an active methylene and are raw materials for arylide yellow dyes, were individually added to the culture of a 3-DAA-producing actinomycete. When their metabolites were analyzed, each expected compound with a phenyldiazenyl moiety was detected in the culture extract. Moreover, we established a one-pot in vitro enzymatic production system for the same phenyldiazene derivatives using a highly reactive diazotase, CmaA6. These results showed that the diazo group of natural products is an attractive tool for expanding the structural diversity of natural products both in vivo and in vitro.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453954","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