ChemBioChem最新文献_第7页

The Anti-Cancer Stem Cell Properties of Copper(II)-Terpyridine Complexes with Attached Salicylaldehyde Moieties. 附有水杨醛分子的铜(II)-三联吡啶配合物的抗癌干细胞特性。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-14 DOI: 10.1002/cbic.202400703

Karampal Singh, Joshua Northcote-Smith, Xiao Feng, Kuldip Singh, Kogularamanan Suntharalingam

{"title":"The Anti-Cancer Stem Cell Properties of Copper(II)-Terpyridine Complexes with Attached Salicylaldehyde Moieties.","authors":"Karampal Singh, Joshua Northcote-Smith, Xiao Feng, Kuldip Singh, Kogularamanan Suntharalingam","doi":"10.1002/cbic.202400703","DOIUrl":"10.1002/cbic.202400703","url":null,"abstract":"We report the synthesis, characterisation, and anti-breast cancer stem cell (CSC) properties of two copper(II)-terpyridine complexes with bidentate salicylaldehyde moieties (2-hydroxybenzaldehyde for 1 and 2-hydroxy-1-naphthaldehyde for 2). The copper(II)-terpyridine complexes 1 and 2 are stable in biologically relevant aqueous solutions and display micromolar potency towards breast CSCs. The most effective complex 1 is 5-fold and 6.6-fold more potent towards breast CSCs than salinomycin and cisplatin, respectively. The copper(II)-terpyridine complexes 1 and 2 also decrease the formation and viability of three-dimensionally cultured mammospheres within the micromolar range. Notably complex 1 is up to 7-fold more potent towards mammospheres than salinomycin or cisplatin. Mechanistic studies suggest that the copper(II)-terpyridine complexes 1 and 2 are able to readily enter breast CSCs, elevate intracellular reactive oxygen species levels, induce DNA damage (presumably by oxidative DNA cleavage), and evoke apoptosis that is independent of caspases. This study shows that the copper(II)-terpyridine motif is a useful building block for the design of anti-breast CSC agents and reinforces the therapeutic potential of copper coordination complexes.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453955","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

Determinants of Product Outcome in Two Sesquiterpene Synthases from the Thermotolerant Bacterium Rubrobacter radiotolerans. 耐热细菌 Rubrobacter radiotolerans 的两种四萜合成酶产物结果的决定因素。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-14 DOI: 10.1002/cbic.202400672

Joshua N Whitehead, Nicole G H Leferink, Sam Hay, Nigel S Scrutton

{"title":"Determinants of Product Outcome in Two Sesquiterpene Synthases from the Thermotolerant Bacterium Rubrobacter radiotolerans.","authors":"Joshua N Whitehead, Nicole G H Leferink, Sam Hay, Nigel S Scrutton","doi":"10.1002/cbic.202400672","DOIUrl":"10.1002/cbic.202400672","url":null,"abstract":"Rubrobacter radiotolerans nerolidol synthase (NerS) and trans-α-bergamotene synthase (BerS) are among the first terpene synthases (TPSs) discovered from thermotolerant bacteria, and, despite sharing the same substrate, make terpenoid products with different carbon scaffolds. Here, the potential thermostability of NerS and BerS was investigated, and NerS was found to retain activity up to 55 °C. A library of 22 NerS and BerS variants was designed to probe the differing reaction mechanisms of NerS and BerS, including residues putatively involved in substrate sequestration, cation-π stabilisation of reactive intermediates, and shaping of the active site contour. Two BerS variants showed improved in vivo titres vs the WT enzyme, and also yielded different ratios of the related sesquiterpenoids (E)-β-farnesene and trans-α-bergamotene. BerS-L86F was proposed to encourage substrate isomerisation by cation-π stabilisation of the first cationic intermediate, resulting in a greater proportion of trans-α-bergamotene. By contrast, BerS-S82L significantly preferred (E)-β-farnesene formation, attributed to steric blocking of the isomerisation step, consistent with what has been observed in several plant TPSs. Our work highlights the importance of isomerisation as a key determinant of product outcome in TPSs, and shows how a combined computational and experimental approach can characterise TPSs and variants with improved and altered functionality.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453945","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

Human 8-Oxoguanine Glycosylase OGG1 Cleaves Abasic Sites and Covalently Conjugates to 3'-DNA Termini via Cysteine and Histidine Addition. 人类 8-氧鸟嘌呤糖基化酶 OGG1 通过半胱氨酸和组氨酸的加成作用裂解消融位点并与 3'-DNA 端部共价结合。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-10 DOI: 10.1002/cbic.202400705

Cameron Bryan, Kun Yang

引用次数: 0

An Expanded Substrate Spectrum of Sulfide:Quinone Oxidoreductase Found in Pollutant Degrading Bacteria. 污染物分解细菌中发现的硫化物：醌氧化还原酶的底物谱扩大了。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-10 DOI: 10.1002/cbic.202400593

Shiqi Fang, Jinfeng Lu, Wenwen Zhou, Chao Sun, Guoqing Chen, Yuhang Tang, Dongzhi Chen, Jun Li

{"title":"An Expanded Substrate Spectrum of Sulfide:Quinone Oxidoreductase Found in Pollutant Degrading Bacteria.","authors":"Shiqi Fang, Jinfeng Lu, Wenwen Zhou, Chao Sun, Guoqing Chen, Yuhang Tang, Dongzhi Chen, Jun Li","doi":"10.1002/cbic.202400593","DOIUrl":"10.1002/cbic.202400593","url":null,"abstract":"Sulfide:Quinone Oxidoreductase (Sqr) Catalyzes The Initial Procedure On Sulfide Transformation, Alongside Sulfide (H2S, S2-) Oxidization Coupled With Coenzyme Q (Coq) Reducing And Reactive Sulfur Species (RSS) Production. Here, We Assessed The Reactivity Of Propanethiol (PT) As An Alternative Substrate For Sqr To Maintain Intracellular Homeostasis In Strain S-1 Capable Of Degrading Emerging Sulfur-Containing Pollutants. We Deleted A Gene Encoding Sqr, And Serial Transcriptional Difference Induced By RSS Dynamics Was Therefore Revealed. Next, The Reaction Properties Of Two Sqr Homologs From Strains JMP134 And S-1 Were Comparatively Characterized, Respectively. As A Result, An Additional Role Of Sqr In Yielding RSS From PT Was Found In Reaction Mixture Prepared By Cell-Free Extracts Or Purified Enzymes. Interestingly, The Transformation Velocity Of PT By Sqr Was Slower Than That Of Sulfides. From This Scenario, It Was A Rate-Determining Step That PT As A Nucleophilic Compound Can Be Added Into Sqr Cysteine To Form Disulfide Bond And Likely Serve Nonoptimal Sulfur Recipient. In Addition, The Role Of Persulfidation Driven By RSS In Combating Oxidative And Sulfur Stresses Required To Be Further Clarified. Nevertheless, This Promiscuity Of Sqr-Binding Organosulfur Compounds And Its Catalytic Modulation Underscored That Expanded Substrates Might Benefit Sulfide Homeostasis In Thiol-Degrading Bacteria.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454029","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

Multidrug Resistance Reversed by Maleimide Interactions. A Biological and Synthetic Overview for an Emerging Field. 马来酰亚胺相互作用逆转的多药耐药性。新兴领域的生物学和合成概述。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-09 DOI: 10.1002/cbic.202400640

Edson D Hernández-Velázquez, Angélica Granados-López, Jesús A López, César R Solorio-Alvarado

{"title":"Multidrug Resistance Reversed by Maleimide Interactions. A Biological and Synthetic Overview for an Emerging Field.","authors":"Edson D Hernández-Velázquez, Angélica Granados-López, Jesús A López, César R Solorio-Alvarado","doi":"10.1002/cbic.202400640","DOIUrl":"https://doi.org/10.1002/cbic.202400640","url":null,"abstract":"Multidrug Resistance (MDR) can be considered one of the most frightening adaptation types in bacteria, fungi, protozoa, and eukaryotic cells. It allows the organisms to survive the attack of many drugs used in the daily basis. This force the development of new and more complex, highly specific drugs to fight diseases. Given the high usage of medicaments, poor variation in active chemical cores, and self-medication, the appearance of MDR is more frequent each time, and has been established as a serious medical and social problem. Over the years it has been possible the identification of several genes and proteins responsible for MDR and with that the development of blockers of them to reach MDR reversion and try to avoid a global problem. These mechanisms also have been observed in cancer cells, and several calcium channel blockers have been successful in MDR reversion, and the maleimide can be found included in them. In this review we explore the history, mechanisms, reversion efforts, and we specifically focused on the maleimide synthesis as MDR-reversers in co-administration, as well as their biological applications in a urge to expand the available information and explore a very plausible MDR reversion source.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386642","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

A Spectroscopic Study on the Amyloid-β Interaction with Clicked Peptide-Porphyrin Conjugates: a Vision Toward the Detection of Aβ Peptides in Aqueous Solution. 淀粉样蛋白-β与点击肽-卟啉共轭物相互作用的光谱研究：水溶液中 Aβ 肽的检测展望。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-09 DOI: 10.1002/cbic.202400431

Rita Tosto, Stefania Zimbone, Giuseppina Sabatino, Giuseppe Di Natale, Maria Laura Giuffrida, Marianna Flora Tomasello, Luca Lanzanò, Tiziana Campagna, Sonia Covaceuszach, Graziella Vecchio, Giuseppe Pappalardo

{"title":"A Spectroscopic Study on the Amyloid-β Interaction with Clicked Peptide-Porphyrin Conjugates: a Vision Toward the Detection of Aβ Peptides in Aqueous Solution.","authors":"Rita Tosto, Stefania Zimbone, Giuseppina Sabatino, Giuseppe Di Natale, Maria Laura Giuffrida, Marianna Flora Tomasello, Luca Lanzanò, Tiziana Campagna, Sonia Covaceuszach, Graziella Vecchio, Giuseppe Pappalardo","doi":"10.1002/cbic.202400431","DOIUrl":"10.1002/cbic.202400431","url":null,"abstract":"Alzheimer's disease (AD) is a multifactorial form of dementia mainly affecting people in the elderly, but no effective cure is available. According to the amyloid hypothesis the aggregation of Amyloid-β (Aβ) into oligomeric toxic species is believed to concur with the onset and progression of the disease heavily. By using a click chemistry approach, we conjugated a suitable designed peptide sequence to a metalloporphyrin moiety to obtain three hybrid peptide systems to be studied for their interaction with Amyloid-β peptides. The aim is to get new tools for the diagnosis and therapy in AD. The results described in this study, which were obtained through spectroscopic techniques (UV-Vis, CD, bis-Ans and intrinsic porphyrin Fluorescence), Microfluidics (GCI) and cell biology (MTT, Live cell imaging and flow cytometry), reveal interesting features about the structure-activity relationships connecting these conjugates with the interaction with Aβ, as well as on their potential use as sensing systems. In our opinion the data reported in this paper make the porphyrin-peptide conjugates highly compelling for further exploration as spectroscopic probes to detect Aβ biomarkers in biological fluids.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386639","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

Mono-Palmitoyl-N-Alkylurea Ligands as Specific Activators of Human Toll-Like Receptor 2/6 Heterodimer. 单棕榈酰-N-烷基脲配体作为人类 Toll 样受体 2/6 异源二聚体的特异性激活剂。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-09 DOI: 10.1002/cbic.202400583

Marjolein M E Isendoorn, Giulia Castello, Çağla Koç, Nico Meeuwenoord, Jeroen D C Codée, Ferry Ossendorp, Dmitri V Filippov

{"title":"Mono-Palmitoyl-N-Alkylurea Ligands as Specific Activators of Human Toll-Like Receptor 2/6 Heterodimer.","authors":"Marjolein M E Isendoorn, Giulia Castello, Çağla Koç, Nico Meeuwenoord, Jeroen D C Codée, Ferry Ossendorp, Dmitri V Filippov","doi":"10.1002/cbic.202400583","DOIUrl":"10.1002/cbic.202400583","url":null,"abstract":"Ligands for Toll-like-receptor 2 (TLR2) have demonstrated significant potential as immune-stimulating components in synthetic vaccines. Activation of TLR2 relies on the formation of dimeric complexes with either TLR1 or TLR6 and the nature of these dimers can impact therapeutic outcomes. The lipopeptide-based TLR2 ligands Pam3CysSK4 and Pam2CysSK4 have been extensively studied, and their recognition by different TLR-receptor heterodimers, TLR2/TLR1 and TLR2/TLR6, respectively, has been established. However, the high lipophilicity of these ligands, containing multiple palmitoyl residues, can result in solubility issues when used as vaccine adjuvants. To address this, we previously synthesized a less lipophilic ligand containing a single palmitoyl chain called mini-UPam, which effectively stimulates human moDC maturation. We here probe the receptor-dimer specificity of several mini-Upam derivatives and reveal that these mini-UPam are hTLR2/TLR6 selective ligands and that the introduction of longer urea alkyl chains does not shift the binding specificity to hTLR2/TLR1 heterodimers, in contrast to their Pam2CysSK4 and Pam3CysSK4 counterparts, pointing to a different binding mode of the UPam ligands.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386641","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

Covalent Modification of Protein by Chemical Probe in Living Cells for Structural and Interaction Studies. 在活细胞中通过化学探针对蛋白质进行共价修饰，以进行结构和相互作用研究。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-08 DOI: 10.1002/cbic.202400715

Zhenxiang Zheng, Yuyu Cheng, Pengfei Li, Chris Soon Heng Tan

{"title":"Covalent Modification of Protein by Chemical Probe in Living Cells for Structural and Interaction Studies.","authors":"Zhenxiang Zheng, Yuyu Cheng, Pengfei Li, Chris Soon Heng Tan","doi":"10.1002/cbic.202400715","DOIUrl":"10.1002/cbic.202400715","url":null,"abstract":"Cellular activities are predominantly carried out by proteins that can dynamically adopt different structural conformations and differentially interact with other biomolecules according to cellular needs. Chemical probes are small molecules used to selectively interact and modulate the activities of specific proteins to study their functions such as the validation of potential drug targets. The remarkable performance of AlphaFold algorithms in the prediction of protein structures has pivoted interest toward elucidating the intracellular dynamics of protein structural conformation where covalent modification of proteins by chemical probes could be used to shed light upon. However, due to the barrier to entry by cell membrane and the general unfavorable reactive conditions of the intracellular environment, most studies using reactive chemical probes are still conducted on purified proteins and cell lysates. Nevertheless, recent progresses have been made in designing chemical probes with improved membrane permeability, stability and reactivity. This paper surveys the literature on recent advancements in membrane-permeable chemical probes and their applications with protein mass spectrometry for the intracellular studies of protein structural conformations and biomolecular interactions.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386640","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

Selenium(II)-Nitrogen Exchange (SeNEx) Chemistry: A Good Chemistry Suitable for Nanomole-Scale Parallel Synthesis, DNA-encoded Library Synthesis and Bioconjugation. 硒（II）-氮交换（SeNEx）化学：一种适用于纳米级平行合成、DNA编码库合成和生物连接的良好化学。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-08 DOI: 10.1002/cbic.202400641

Wei Hou, Shaoneng Hou, Yuang Gu, Shuning Zhang, Peixiang Ma, Hai-Yu Hu, Hongtao Xu

引用次数: 0

Whole-Cell Biotransformation for the Preparation of Chromopyrrolic Acid and 5,5'-dichloro-Chromopyrrolic Acid in Escherichia coli. 在大肠杆菌中通过全细胞生物转化制备铬吡咯烷酮酸和 5,5'-二氯铬吡咯烷酮酸。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-10-07 DOI: 10.1002/cbic.202400718

Lingyue Wang, Shilong Wei, Mengtie Guan, Yan Li, Xikang Zheng, Zhengren Xu

引用次数: 0