ChemBioChem最新文献_第5页

Chromenone derivatives as CRM1 Inhibitors for Targeting Glioblastoma. 染色质衍生物作为靶向胶质母细胞瘤的CRM1抑制剂。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-23 DOI: 10.1002/cbic.202500195

Wolfgang Link, Salvatore Princiotto, Lucía Jiménez, Lucía Domínguez, João G N Sequeira, Cristiana Mourato, Alba Orea-Soufi, Bruno Santos, Sabrina Dallavalle, Miguel Machuqueiro, Bibiana I Ferreira

{"title":"Chromenone derivatives as CRM1 Inhibitors for Targeting Glioblastoma.","authors":"Wolfgang Link, Salvatore Princiotto, Lucía Jiménez, Lucía Domínguez, João G N Sequeira, Cristiana Mourato, Alba Orea-Soufi, Bruno Santos, Sabrina Dallavalle, Miguel Machuqueiro, Bibiana I Ferreira","doi":"10.1002/cbic.202500195","DOIUrl":"https://doi.org/10.1002/cbic.202500195","url":null,"abstract":"Glioblastoma (GBM) is one of the most aggressive and deadly cancers. Due to the complexity and redundancy within signaling networks in GBM, targeted inhibitors of specific pathways have shown only limited success. The nuclear export receptor Chromosome Region Maintenance 1 (CRM1) has recently emerged as a promising therapeutic target, as its inhibition can simultaneously disrupt multiple key oncogenic drivers. In this study, we explore whether chromenone derivatives, known for detecting thiol-containing molecules, can function as CRM1 inhibitors. We synthesized several chromenone-based derivatives and demonstrated that they inhibit CRM1-driven nuclear export in a structure- and dose-dependent manner. A preliminary structure-activity relationship (SAR) was established, providing a rationale for selective CRM1 binding based on molecular docking studies. Additionally, we showed that the active chromenone derivatives effectively inhibit the nuclear export of endogenous nuclear export signal (NES)-containing substrates in glioblastoma cells. Several of these compounds exhibit selective cytotoxicity against glioblastoma cell lines, highlighting their potential as targeted therapies for GBM.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500195"},"PeriodicalIF":2.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961571","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

Visual Detection and Identification of Influenza A Viruses by Nucleic Acid Probe-Enabled Lateral Flow Assay. 核酸探针侧流法检测和鉴定甲型流感病毒。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-23 DOI: 10.1002/cbic.202500216

Zhihao Xu, Xiaowei Ma, Jing Ye, Pengfei Hou, Caiqing Yuan, Li Pan, Donglei Yang, Xue Li, Pengfei Wang

{"title":"Visual Detection and Identification of Influenza A Viruses by Nucleic Acid Probe-Enabled Lateral Flow Assay.","authors":"Zhihao Xu, Xiaowei Ma, Jing Ye, Pengfei Hou, Caiqing Yuan, Li Pan, Donglei Yang, Xue Li, Pengfei Wang","doi":"10.1002/cbic.202500216","DOIUrl":"https://doi.org/10.1002/cbic.202500216","url":null,"abstract":"Diagnosis of influenza A viral infection is crucial for preventing disease transmission and providing effective clinical treatments. There is an increasing need for convenient detection methods to enable simple yet precise identification of viral infections. Herein, a nucleic acid probe-enabled lateral flow assay (NALFA) is developed to realize visual detection and identification of influenza A viral infections (H1N1 and H3N2) of high sensitivity and specificity. Viral RNA targets are recognized by a padlock probe, which is circularized to induce rolling circle amplification (RCA). RCA products are enzymatically cleaved into short amplicons to complex with capture DNA probes for gold colloidal-induced visual lateral flow assay. NALFA achieved attomolar (aM) sensitivity for both standard viral RNAs, along with high specificity. While applying clinical samples (16 H1N1 patients, 12 healthy controls), NALFA exhibited high detection accuracy to successfully discriminate infected samples from noninfected samples. NALFA represents a potent and convenient nucleic acid detection assay that shall find its applications in fields of viral detection and beyond.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500216"},"PeriodicalIF":2.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958584","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 Enzymes and Chemoenzymatic Synthesis of Tetrasaccharide Linkage Region of Proteoglycans. 蛋白聚糖四糖键区的酶及化学酶合成研究进展。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-23 DOI: 10.1002/cbic.202500095

Po-Han Lin, Xuefei Huang

引用次数: 0

NMR Pure Shift Spectroscopy and Its Potential Applications in the Pharmaceutical Industry. 核磁共振纯位移光谱及其在制药工业中的潜在应用。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-22 DOI: 10.1002/cbic.202401012

Mengjie Qiu, Wen Zhu, Xiaoxu Zheng, Zhong Chen, Yanqin Lin

引用次数: 0

Artificial Enzyme Design with Novel Functions via Site-Specific Chemical Modification. 通过位点特异性化学修饰设计具有新功能的人工酶。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-22 DOI: 10.1002/cbic.202500075

Zhixi Zhu, Zhi Zhou

引用次数: 0

Front Cover: Site-Specific Modification of Native IgGs with Flexible Drug-Load (ChemBioChem 8/2025) 封面：具有柔性药物负载的天然igg的位点特异性修饰（ChemBioChem 8/2025）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-18 DOI: 10.1002/cbic.202580801

Jöri E. Wehrmüller, Julia C. Frei, Torsten Hechler, Michael Kulke, Andreas Pahl, Martin Béhé, Roger Schibli, Philipp R. Spycher

引用次数: 0

A Recognition Tag of Human Origin for Bioorthogonal Generation of Antibody-Drug Conjugates using Microbial Biotin Ligase. 利用微生物生物素连接酶正交生成抗体-药物偶联物的人类来源识别标签。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-17 DOI: 10.1002/cbic.202500261

Peter Bitsch, Sebastian Bitsch, Noah Murmann, Ingo Bork, Janine Becker, Harald Kolmar

{"title":"A Recognition Tag of Human Origin for Bioorthogonal Generation of Antibody-Drug Conjugates using Microbial Biotin Ligase.","authors":"Peter Bitsch, Sebastian Bitsch, Noah Murmann, Ingo Bork, Janine Becker, Harald Kolmar","doi":"10.1002/cbic.202500261","DOIUrl":"https://doi.org/10.1002/cbic.202500261","url":null,"abstract":"The use of enzymes, such as microbial transglutaminase, lipoate protein ligase A, or sortase A, for the generation of antibody-drug conjugates has proven to be a powerful tool for the site-specific payload conjugation to tumor-specific antibodies. Herein, the extension of this enzymatic toolbox by Pyrococcus horikoshii biotin ligase is reported. To this end, the therapeutic antibody trastuzumab is equipped with p67, the 67 amino acid carboxyl-terminal domain of human propionyl-CoA carboxylase α subunit, at the C-terminus of either the light or heavy chain (Trz-LC:p67 and Trz-HC:p67). Upon incubation with PhBL, the azide-bearing linker desthiobiotin azide is site-specifically coupled to the p67 domains at the antibody. Subsequent strain-promoted azide-alkyne cycloaddition with DBCO-AF488 and DBCO-Val-Cit-PAB-MMAE yielded conjugates near to full conversion. In cellular assays, these constructs exhibit single-digit nanomolar EC50 values in cellular proliferation assays on SK-BR-3 and A431 cells, where no significant difference in the performance between the two variants Trz-LC:p67-MMAE and Trz-HC:p67-MMAE is observed. On high Fc-γIIIa receptor expressing Jurkat cells, Trz-HC:p67-MMAE exhibits higher potency than Trz-LC:p67-MMAE, indicating an Fc-blocking effect of p67 when fused to the light chain.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500261"},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958704","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

Identification of Key Active-Site Positions Controlling the Chemoselectivity of Aspergillus Brasiliensis Unspecific Peroxygenase. 控制巴西曲霉非特异性过氧酶化学选择性关键活性位点的鉴定

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-17 DOI: 10.1002/cbic.202500181

Fabian Schmitz, Maike Hoffrogge, Katja Koschorreck, Yasuhisa Fukuta, Alessandra Raffaele, Florian Tieves, Thomas Hilberath, Frank Hollmann, Vlada B Urlacher

{"title":"Identification of Key Active-Site Positions Controlling the Chemoselectivity of Aspergillus Brasiliensis Unspecific Peroxygenase.","authors":"Fabian Schmitz, Maike Hoffrogge, Katja Koschorreck, Yasuhisa Fukuta, Alessandra Raffaele, Florian Tieves, Thomas Hilberath, Frank Hollmann, Vlada B Urlacher","doi":"10.1002/cbic.202500181","DOIUrl":"https://doi.org/10.1002/cbic.202500181","url":null,"abstract":"Heme-containing unspecific peroxygenases (UPOs) have attracted significant attention as biocatalysts for oxidation reactions due to their ability to function without expensive nicotinamide cofactors. In the recent study, the UPO from aspergillus brasiliensis (AbrUPO) is found to catalyze the aromatic hydroxylation of substituted benzenes, a feature that distinguishes AbrUPO from other reported wild-type UPOs. To elucidate the underlying factors in the active site and substrate access channel of AbrUPO-which contains fewer phenylalanine residues compared to other UPOs that primarily catalyze benzylic hydroxylation-twenty two AbrUPO variants with single, double, triple, or quadruple amino acid substitutions were constructed to mimic the active sites or substrate access channels of other UPOs. A number of mutated variants exhibited altered activity and selectivity, and several positions were identified that influence enzyme chemoselectivity. Among them, substitution of alanine at position 186 with bulkier residues such as phenylalanine or leucine lead to a shift in chemoselectivity toward alkyl chain hydroxylation of substituted benzenes. Molecular docking studies indicated that the A186F mutation restricts the flexibility and reorientation of ethylbenzene in the active site of AbrUPO, thereby preventing oxidation at the aromatic ring while promoting benzylic hydroxylation.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500181"},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954194","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

The Position of Indole Methylation Controls the Structure, DNA Binding, and Cellular Functions of Mithramycin SA-Trp Analogues. 吲哚甲基化位置控制米霉素SA-Trp类似物的结构、DNA结合和细胞功能。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-17 DOI: 10.1002/cbic.202401084

Caixia Hou, Suhas Bhosale, Kazuto Yasuda, Rajesh Yetirajam, Markos Leggas, Jürgen Rohr, Oleg V Tsodikov

{"title":"The Position of Indole Methylation Controls the Structure, DNA Binding, and Cellular Functions of Mithramycin SA-Trp Analogues.","authors":"Caixia Hou, Suhas Bhosale, Kazuto Yasuda, Rajesh Yetirajam, Markos Leggas, Jürgen Rohr, Oleg V Tsodikov","doi":"10.1002/cbic.202401084","DOIUrl":"https://doi.org/10.1002/cbic.202401084","url":null,"abstract":"Mithramycin (MTM) is a polyketide anticancer natural product, which functions by noncovalent binding to DNA in the minor groove without intercalation, resulting in inhibiting transcription at G/C-rich promoters. MTM is a potent inhibitor of cancer cells, such as Ewing sarcoma, driven by abnormal fusions involving E26 transformation-specific (ETS) family transcription factors friend leukemia integration 1 (FLI1) and ETS-related gene (ERG). However, MTM is rather toxic and nonselective; therefore, safer, selective analogues of MTM are required for use in the clinic as anticancer drugs. Herein, by using a combination of X-ray crystallographic, biophysical, and cell and molecular biological techniques, the structural and functional consequences of 3-side chain methylation at positions 5, 6, and 7 of the indole ring of the potent analogue MTM SA-Trp are explored. The conformation of the analogues in complexes with DNA, their DNA binding function, cytotoxicity, selectivity, and potency as transcription antagonists depended on the position of the methylation. MTM SA-5-methyl-Trp emerged as the most selective analogue, presumably due to the right balance of the DNA binding and the solvent exposure of the 3-side chain. This study demonstrates that minor chemical changes can have strong effects in analogue development and paves the way to further development of next-generation MTM analogues.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2401084"},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957802","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: The Biarylitides: Understanding the Structure and Biosynthesis of a Fascinating Class of Cytochrome P450 Modified RiPP Natural Products (ChemBioChem 7/2025) 封面：The biarylides：了解一类迷人的细胞色素P450修饰的RiPP天然产物的结构和生物合成（ChemBioChem 7/2025）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-16 DOI: 10.1002/cbic.202580701

Leo Padva, Jemma Gullick, Laura J. Coe, Mathias H. Hansen, James J. De Voss, Max Crüsemann, Max J. Cryle

引用次数: 0