ChemBioChem最新文献_第4页

Boosting Antibiotic Efficacy of Azole Drugs against Methicillin-Resistant Staphylococcus Aureus by Coordination to Rhenium Carbonyl Complexes. 通过配位铼羰基配合物提高唑类药物对耐甲氧西林金黄色葡萄球菌的抗菌效果。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-25 DOI: 10.1002/cbic.202500368

Kevin Schindler, Gozde Demirci, Bettina Tran, Sara Nasiri Sovari, Youri Cortat, Nicolas F Rosa De Sousa, Carola Velti, Baptiste Chapuis, Aurélien Crochet, Aleksandar Pavic, Jelena Djuris, Stefan Salentinig, Fabio Zobi

{"title":"Boosting Antibiotic Efficacy of Azole Drugs against Methicillin-Resistant Staphylococcus Aureus by Coordination to Rhenium Carbonyl Complexes.","authors":"Kevin Schindler, Gozde Demirci, Bettina Tran, Sara Nasiri Sovari, Youri Cortat, Nicolas F Rosa De Sousa, Carola Velti, Baptiste Chapuis, Aurélien Crochet, Aleksandar Pavic, Jelena Djuris, Stefan Salentinig, Fabio Zobi","doi":"10.1002/cbic.202500368","DOIUrl":"10.1002/cbic.202500368","url":null,"abstract":"Herein, a library of rhenium di- and tricarbonyl complexes featuring various antimicrobial azoles as monodentate ligands is synthesized and characterized. Their antimicrobial activity is evaluated against both methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), and selected compounds are also assessed for cytotoxicity, yielding promising therapeutic indices. Notably, the complexation of antifungal azoles to the rhenium core enhances antimicrobial efficacy, with a compound exhibiting up to a 32-fold improvement in minimum inhibitory concentration (MIC) values relative to the parent azole. Structure-activity relationships indicate that cationic fac-[Re(CO)3]+ complexes consistently outperform their cis-[Re(CO)2]+ counterparts, and mechanistic studies suggest that active complexes disrupt bacterial membrane integrity and interfere with the electron transport chain. Complementary small-angle X-ray scattering and in silico analysis corroborate these findings, offering insights into the mechanism of action of this family of complexes.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500368"},"PeriodicalIF":2.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482682","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

Pancatalytic Tumor Therapy by Ultrasound Activation of Inorganic Sonosensitizers. 无机超声敏化剂的超声活化胰脏肿瘤治疗。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-24 DOI: 10.1002/cbic.202500440

Furong Cheng, Yu Tian, Yu Chen

{"title":"Pancatalytic Tumor Therapy by Ultrasound Activation of Inorganic Sonosensitizers.","authors":"Furong Cheng, Yu Tian, Yu Chen","doi":"10.1002/cbic.202500440","DOIUrl":"10.1002/cbic.202500440","url":null,"abstract":"Pancatalytic therapy (PCT) is a comprehensive framework for disease management through the holistic control of catalytic and quasi-catalytic processes, including preparation (P) of catalysts, activation (A) of specific bio-effects, and nontoxic treatment (N) of different diseases. Ultrasound (US)-activated inorganic sonosensitizers have emerged as a powerful platform for pancatalytic tumor therapy, enabling precise and noninvasive cancer treatment through localized reactive oxygen species (ROS) generation by the specific sonocatalytic mechanism. Upon exposure to US activation, inorganic sonosensitizers generate electron-hole pairs that produce sonocatalytic effect, generating cytotoxic ROS to induce oxidative damage in tumor cells. With ongoing advances in nanomaterial design and US technology, inorganic sonosensitizers represent a transformative approach for precision oncology, offering a versatile and clinically translatable solution for the emerging pancatalytic tumor eradication. This comprehensive review summarizes and highlights recent developments in different kinds of inorganic sonosensitizers and their specific application for pancatalytic tumor therapy. This review begins with providing an overview of inorganic sonosensitizers. The focus is then shifted to US-activated pancatalytic tumor therapy with high therapeutic efficacy. The biosafety and biospecificity of US-activated sonosensitizers in combating tumor are further discussed. Finally, the critical challenges and perspectives on potential directions for future clinical translation of this technology are presented.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500440"},"PeriodicalIF":2.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482684","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

In Vivo Biosynthesis and Direct Incorporation of Non-Canonical Amino Acids into Proteins. 非典型氨基酸在体内的生物合成和直接掺入蛋白质。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-24 DOI: 10.1002/cbic.202500282

Ivana Drienovska, Jan Hendrik Illies, T Moritz Weber

引用次数: 0

2-oxoglutarate analogue-based biomolecular tools for exploring structure-activity relationships in non-heme iron enzymes. 基于2-氧戊二酸类似物的生物分子工具，用于探索非血红素铁酶的结构-活性关系。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-22 DOI: 10.1002/cbic.202500177

Peter Windsor, Sourav Chatterjee, Anoop Rama Damodaran, Ambika Bhagi-Damodaran

{"title":"2-oxoglutarate analogue-based biomolecular tools for exploring structure-activity relationships in non-heme iron enzymes.","authors":"Peter Windsor, Sourav Chatterjee, Anoop Rama Damodaran, Ambika Bhagi-Damodaran","doi":"10.1002/cbic.202500177","DOIUrl":"https://doi.org/10.1002/cbic.202500177","url":null,"abstract":"2-oxoglutarate (2OG)-dependent non-heme iron (NHFe) enzymes constitute a family of enzymes that use 2OG and oxygen to catalyze the hydroxylation of unactivated C(sp3)-H bonds. These enzymes are of biological importance and therapeutic interest due to their role in regulating various cellular processes. Herein, we have rationally designed two classes of 2OG analogues and have used them as tools to investigate the active site of a 2OG-dependent NHFe enzyme, prolyl hydroxylase domain 2 (PHD2). Using an activity assay in conjunction with steady-state kinetics, we identify a new class of aryl-conjugated 2OG analogues that exhibit 12-fold varied inhibition and compete with 2OG for the PHD2 active site. Immunoblot studies suggest that these analogues are biologically active and could target PHD2 intracellularly. Furthermore, computational modelling studies reveal that the analogues bind to the active site in a \"flipped\" conformation relative to 2OG, and functional group placement is responsible for their different inhibition capabilities. Our mutagenesis studies further validate this unique binding mode and suggest several interactions that are crucial for inhibition. Overall, these studies provide a toolkit of 2OG analogues to establish structure-activity relationships and identify interactions that could be useful for PHD2 inhibitor design.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500177"},"PeriodicalIF":2.6,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367697","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

An Oxyprenylated Phenylpropanoid Pharmacologic Scaffold for SelU Inhibition. 一种抑制SelU的氧丙烯化苯丙类药物支架。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-20 DOI: 10.1002/cbic.202500280

Stephen J Dansereau, Alexander Shekhtman, Salvatore Genovese, Chiara Collevecchio, Serena Fiorito, Thomas J Begley, Francesco Epifano, Jia Sheng

{"title":"An Oxyprenylated Phenylpropanoid Pharmacologic Scaffold for SelU Inhibition.","authors":"Stephen J Dansereau, Alexander Shekhtman, Salvatore Genovese, Chiara Collevecchio, Serena Fiorito, Thomas J Begley, Francesco Epifano, Jia Sheng","doi":"10.1002/cbic.202500280","DOIUrl":"10.1002/cbic.202500280","url":null,"abstract":"MnmH, better known as tRNA 2-selenouridine synthase (SelU), is a member of the Mnm family enzymes that work in concert to modify uridine at the wobble position. Instrumental in maintaining base pair fidelity and exclusive to bacteria, SelU is a promising drug target. Although no molecular structure has been experimentally calculated, insights into this enzyme's mechanism of catalysis have been empirically gleaned and proven useful for ligand-based rational drug design. In this study, a small group of natural and semisynthetic oxyprenylated phenylpropanoids were selected based on their compositional resemblance to the purported SelU ligands. Specifically, these compounds contained one or more geranyl groups branching from aromatic frameworks, all of which are believed to heighten affinity to SelU. Meticulous screening of each compound against an N-terminal SelU construct via fluorescence quenching of W83 further reveals details on the enzyme-substrate binding mode. Conformational flexibility of residues around W83 is suggested by the slow bimolecular quenching constants calculated for each compound. This is consistent with the single binding site and the blend of interaction-types calculated at the active site. Lastly, this general oxyprenylated framework, along with a cinnamic acid moiety, is established as a pharmacologic scaffold that can be further optimized into potential antibiotics.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500280"},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332182","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

Front Cover: β-Turn Mimicking Crosslinking Provides Hyperstability and Fast Folding Kinetics for Short Collagen Triple Helices (ChemBioChem 12/2025) 封面：β-转模拟交联提供超稳定性和快速折叠动力学的短胶原蛋白三螺旋（ChemBioChem 12/2025）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-19 DOI: 10.1002/cbic.202581201

Pengfei Jin, Diane N. Rafizadeh, Huanyi Zhao, Prof. David M. Chenoweth

引用次数: 0

Bioactivity profiles of progressively ring-fluorinated cyclohexyl motifs in the WKYMVm peptide as formylpeptide FPR2 agonists and in keto-piperazines as anti-trypanosome agents. WKYMVm肽中作为甲酰基肽FPR2激动剂的渐进式环氟化环己基序和作为抗锥虫剂的酮哌嗪中的生物活性谱。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-18 DOI: 10.1002/cbic.202500384

David O'Hagan, Mengfan He, Christina M Thomson, Dawn Thompson, Vytautus Kuodis, Terence K Smith, Sergio Dall'Angelo

{"title":"Bioactivity profiles of progressively ring-fluorinated cyclohexyl motifs in the WKYMVm peptide as formylpeptide FPR2 agonists and in keto-piperazines as anti-trypanosome agents.","authors":"David O'Hagan, Mengfan He, Christina M Thomson, Dawn Thompson, Vytautus Kuodis, Terence K Smith, Sergio Dall'Angelo","doi":"10.1002/cbic.202500384","DOIUrl":"https://doi.org/10.1002/cbic.202500384","url":null,"abstract":"A series of all-cis ring fluorinated cyclohexylalanines with progressively increasing levels of vicinal fluorines, as well as 4-fluorophenylalanine and pentafluoroarylphenylalanine were introduced into the WKYMVm peptide in place of its tyrosine residue, for assays against the G-protein coupled formylpeptide receptor, FPR2. Selected all-cis ring cyclohexylalanines of this class were also incorporated into a keto-piperazine molecular scaffold to generate sp3 rich derivatives for assays against the parasite Trypanosoma. brucei. For these cyclohexylalanine analogues bioactivity trends correlated progressively with the levels of fluorination in each of the case studies. Notably, the all-cis pentafluorocyclohexylalanine analogue of the W-peptide was least active perhaps correlating with the well-known polarity of this 'Janus face' cyclohexane. Although the trend was also apparent in the anti-trypanosomal assays of the keto-piperazine derivatives, it was less so and some compounds were more active than the previously reported phenylalanine derived analogue.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500384"},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323954","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

Recent Advances in the Biosynthetic Studies of Sordarin. 丹参素生物合成研究进展。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-18 DOI: 10.1002/cbic.202500402

Yuben Qiao, Ikuro Abe

引用次数: 0

Poly(ethylene Glycol)-Based Peptidomimetics (Pegtides) of Antimicrobial Peptides. 基于聚乙二醇的抗菌肽模拟物（Pegtides）。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-18 DOI: 10.1002/cbic.202500258

Conor Shine, John R F B Connolly, Robert D Murphy, Hazel Lafferty, Abdalmalek Alfnikh, Ned P Buijs, Hawraa Shahrour, Nathaniel I Martin, Eoghan O'Neill, George Amarandei, Jimmy Muldoon, Marc Maresca, Deirdre Fitzgerald-Hughes, Marc Devocelle

引用次数: 0

Regulation of Gene Expression of Mouse D-Amino Acid Oxidase. 小鼠d -氨基酸氧化酶基因表达的调控。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-18 DOI: 10.1002/cbic.202500323

Huong Thi Thanh Trinh, Yuji Shishido, Nam Hoang Tran, Diem Hong Tran, Soo Hyeon Kim, Hirofumi Sogabe, Kiyoshi Fukui

{"title":"Regulation of Gene Expression of Mouse D-Amino Acid Oxidase.","authors":"Huong Thi Thanh Trinh, Yuji Shishido, Nam Hoang Tran, Diem Hong Tran, Soo Hyeon Kim, Hirofumi Sogabe, Kiyoshi Fukui","doi":"10.1002/cbic.202500323","DOIUrl":"https://doi.org/10.1002/cbic.202500323","url":null,"abstract":"D-amino acid oxidase (DAO) catalyzes oxidative deamination of D-amino acids, producing 2-oxo acids, hydrogen peroxide and ammonia. In mammals, DAO is essential for metabolizing both endogenous and exogenous D-amino acids. Our previous studies on human DAO identified two promoter regions (P1 and P2), a negative regulatory element in intron 1, and several transcription factor binding sites. In this study, we investigated the regulatory mechanism of mouse DAO gene expression to compare with the human system. Poly (I:C) or Interleukin-1βtreatment induced DAO expression by 1.8-2.0 folds in the mouse brain, cerebellum and cerebral cortex. To determine the promoter activity in the upstream region of initiation site, we constructed plasmids containing mouse DAO gene fragments inserted into pGL4 [luc2P/Hygro] vector and assessed luciferase activity in LLC-PK1 cells. We analyzed a series of deletion constructs, revealing promoter activity in all tested fragments. The highest promoter activity was detected in the -333/-87 subregion, with residual activities in the -87/+111 region. Bioinformatics analysis identified transcription factors, including NEUR, EGRF, ZF07, ZF11, KLFS, SP1F and ZF02, which bind to both the human and mouse DAO genes at conserved positions, suggesting their critical role in regulating DAO promoter activity.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500323"},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323957","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