ChemBioChem最新文献_第6页

A Diazaborine Activity-Based Sensing Fluorescent Probe Reports Endogenously Produced Mitochondrial Peroxynitrite in Live Macrophages.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-10 DOI: 10.1002/cbic.202400972

Jack G Haggett, G Dinesh Kumar, Michael J Melville, Chelsea G Johansen, Luke D Knudson, Nikki L Farnsworth, Dylan W Domaille

{"title":"A Diazaborine Activity-Based Sensing Fluorescent Probe Reports Endogenously Produced Mitochondrial Peroxynitrite in Live Macrophages.","authors":"Jack G Haggett, G Dinesh Kumar, Michael J Melville, Chelsea G Johansen, Luke D Knudson, Nikki L Farnsworth, Dylan W Domaille","doi":"10.1002/cbic.202400972","DOIUrl":"10.1002/cbic.202400972","url":null,"abstract":"We present the synthesis, properties, and imaging applications of a new class of diazaborine-based probes (Peroxynitrite Probe-1, PNP-1) for selective peroxynitrite (ONOO-) imaging in live cells. PNP-1 features a diazaborine-based reaction motif that provides excellent discrimination between H2O2 and ONOO-, solving a persistent challenge of organoboron-based fluorescent probes for oxidative metabolite imaging. We demonstrate the utility of PNP-1 to detect endogenously produced ONOO- in live RAW 264.7 macrophages by fluorescence microscopy, with probe selectivity confirmed with inhibition of NADPH oxidases and nitric oxide synthase, the requisite enzymatic machinery for ONOO- production. Co-localization studies unexpectedly reveal preferential mitochondrial localization, which we show is dependent on the naphthalimide scaffold. Taken together, our results show that diazaborines are a novel motif for selective ONOO- reactivity, positioning them for incorporation into other ONOO--specific chemical biology tools.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400972"},"PeriodicalIF":2.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595869","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

Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-08 DOI: 10.1002/cbic.202500048

Hannah Fremlén, Björn M Burmann

{"title":"Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases.","authors":"Hannah Fremlén, Björn M Burmann","doi":"10.1002/cbic.202500048","DOIUrl":"10.1002/cbic.202500048","url":null,"abstract":"Cells in all kingdoms of life employ dedicated protein quality control machineries for both their cytosolic and membrane proteome ensuring cellular functionality. These crucial systems consist besides a large variety of molecular chaperones, ensuring a proper fold and consequently function of the client's proteome, of several proteases to clean out damaged, unfunctional and potentially toxic proteins. One of the key features underlying the functional cycle of these quality control systems is the inherent flexibility of their bound clients which for a long time impaired detailed structural characterization, with advanced high-resolution NMR spectroscopy in the last decade playing a key role contributing to the present understanding of their functional properties. Although these studies laid the foundation of the present knowledge of the mechanistic details of the maintenance of cytosolic proteins, the understanding of related systems employed for membrane associated as well as integral membrane proteins remains rather sparse to date. Herein, we review the crucial contributions of structural and dynamical biology approaches, possessing the power to resolve both structure and dynamics of such systems as well as enabling the elucidation of the functional repertoire of multimeric proteases involved in maintaining a functional membrane proteome.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500048"},"PeriodicalIF":2.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584009","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

Cucurbit[7]uril-Styryl dye complexes for Fluorescent Recognition of DNA and Cell Imaging.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-07 DOI: 10.1002/cbic.202400892

Ekaterina Y Chernikova, Maria A Ustimova, Yuri V Fedorov, Polina A Chernikova, Ivan A Godovikov, Nelly S Chmelyuk, Maxim A Abakumov, Olga A Fedorova

{"title":"Cucurbit[7]uril-Styryl dye complexes for Fluorescent Recognition of DNA and Cell Imaging.","authors":"Ekaterina Y Chernikova, Maria A Ustimova, Yuri V Fedorov, Polina A Chernikova, Ivan A Godovikov, Nelly S Chmelyuk, Maxim A Abakumov, Olga A Fedorova","doi":"10.1002/cbic.202400892","DOIUrl":"https://doi.org/10.1002/cbic.202400892","url":null,"abstract":"This paper focused on the DNA-binding properties of novel dicationic cyanine dyes, in which pyridinium centers are linked by bridges of different functionalities. We found that dye 1, bearing a flexible butyl-4-methylpyridinium terminal fragment, has the ability to bind to the DNA groove. The attachment of a quite rigid para-xylylene-4-methylpyridinium unit as a terminal group in dye 2 contributed to dual DNA-binding modes: intercalation and groove binding. We tested the encapsulation ability and the effect on the dye-DNA binding mode by using a synthetic molecular container such as CB[7]. Unexpectedly, monitoring dye-DNA interaction in the presence of CB[7] revealed that dye molecules partially remain in DNA frameworks, even though they had a higher affinity towards CB[7]. In the case of dye 1, the transformation of dimeric forms to the left-handed aggregates to yield a ternary system CB[7]-dye-DNA occurred. For dye 2, reversibility of intercalation and a slight right-handed aggregation templated by DNA are observed. A cytotoxicity and ability of dyes to stain the living cells in their free and encapsulated forms have been investigated. These findings provide useful information about ligand-DNA interactions, which are valuable for the rational design of drug delivery systems and platforms for cellular imaging and therapy.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400892"},"PeriodicalIF":2.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571777","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

Avoiding Misreading During Genetic Reprogramming in mRNA Display.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-07 DOI: 10.1002/cbic.202500083

Gopal K Dubey, Peng-Hsun Chase Chen, Sabrina E Iskandar, Naga Garikiparthy, Hratch J Zokian, Hu-Jung Julie Lee, Adam Weinglass, S Adrian Saldanha, Kenneth K Hallenbeck

引用次数: 0

Lienhwalides: Unique Tropolone-Maleidride Hybrids from Hypoxylon lienhwacheense.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-07 DOI: 10.1002/cbic.202500037

Katharina Schmidt, Esteban Charria-Girón, Tatiana E Gorelik, Christian Kleeberg, Jackson M Muema, Simone Heitkämper, Bart Verwaaijen, Eric Kuhnert, Jennifer Gerke, Jörn Kalinowski, Kevin D Hyde, Marc Stadler, Russell Cox, Frank Surup

{"title":"Lienhwalides: Unique Tropolone-Maleidride Hybrids from Hypoxylon lienhwacheense.","authors":"Katharina Schmidt, Esteban Charria-Girón, Tatiana E Gorelik, Christian Kleeberg, Jackson M Muema, Simone Heitkämper, Bart Verwaaijen, Eric Kuhnert, Jennifer Gerke, Jörn Kalinowski, Kevin D Hyde, Marc Stadler, Russell Cox, Frank Surup","doi":"10.1002/cbic.202500037","DOIUrl":"10.1002/cbic.202500037","url":null,"abstract":"Hypoxylon lienhwacheense, a fungal species with an unclear taxonomic placement within the Hypoxylaceae, presents a highly rare stromatal secondary metabolite profile. Isolation of its major stromatal constituents leads to the discovery of a novel tropolone-maleidride hybrid molecule, lienhwalide A 5, in addition to the known cordyanhydride B 6, its new derivative 7, and binaphthalenetetraol 8. Unexpectedly, Hypoxylon lienhwacheense produces in liquid cultures various lienhwalide A congeners 9-11. Their structures and relative configurations are elucidated using high-resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, with their absolute configurations determined using X-ray analysis of a semisynthetic brominated derivative of 9 and synthesizing α-methoxy-α-trifluoromethylphenylacetyl esters of 11. Feeding experiments with 13C-labeled precursors (13C-methionine; 1-13C- and U-13C6-glucose) reveal insights into the biogenesis of tropolone and maleidride moieties, according to 13C couplings and incredible natural abundance double quantum transfer NMR data. Genome analysis identifies two separate biosynthetic gene clusters responsible for these moieties, and heterologous expression experiments provide further insights into the interplay of both clusters during the biosynthesis of these hybrid natural products. Remarkably, lienhwalides exhibit reduced toxicity and enhance antibacterial selectivity compared to related fungal tropolones.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500037"},"PeriodicalIF":2.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571779","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

Expanding the Substrate Scope of C-N Lyases by Homologue Discovery.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-07 DOI: 10.1002/cbic.202500068

Laura Bothof, Riccardo Iacovelli, Pieter G Tepper, Gerrit J Poelarends

{"title":"Expanding the Substrate Scope of C-N Lyases by Homologue Discovery.","authors":"Laura Bothof, Riccardo Iacovelli, Pieter G Tepper, Gerrit J Poelarends","doi":"10.1002/cbic.202500068","DOIUrl":"10.1002/cbic.202500068","url":null,"abstract":"The aspartase/fumarase superfamily is a group of homologous enzymes that promote the reversible elimination of functional groups from succinyl-containing compounds, typically yielding fumarate as the common product. Over the past 50 years, members of this superfamily have continuously demonstrated their power and significance as biocatalysts. This is exemplified by ethylenediamine-N,N-disuccinic acid (EDDS) lyase, which was shown to have an extraordinary amine scope, enabling the production of a wide variety of N-substituted aspartic acids. In this work, we used this enzyme as a starting point for a homology-based strategy to expand the biocatalytic toolbox of C-N bond-forming enzymes. We selected 13 enzymes for biochemical characterization, and identified several EDDS-lyase homologues that can accept L-amino acids as substrates in the hydroamination of fumarate to produce the corresponding aminopolycarboxylic acids. Lastly, we carried out a sequence similarity network analysis of the aspartase/fumarase superfamily, which suggests that EDDS lyase and its homologues may represent a distinct isofunctional subfamily, laying the foundations for future enzyme discovery and engineering campaigns.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500068"},"PeriodicalIF":2.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571778","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

Genetically Encoded Fluorescent and Bioluminescent Probes for HDAC8.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-06 DOI: 10.1002/cbic.202500096

Ying Wang, Lin Sun, Weimin Xuan

引用次数: 0

Characterization of ActVI-ORF3 and ActVI-ORF4 as Lactonizing and Delactonizing Enzymes in Relation to Metabolic Flux in Actinorhodin Biosynthesis.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-06 DOI: 10.1002/cbic.202500049

Makoto Hashimoto, Kazuki Ishikawa, Yuri Fukushima, Sarina Shimazu, Mizuha Yabuzaki, Yuka Kamezawa, Takaaki Taguchi, Koji Ichinose

{"title":"Characterization of ActVI-ORF3 and ActVI-ORF4 as Lactonizing and Delactonizing Enzymes in Relation to Metabolic Flux in Actinorhodin Biosynthesis.","authors":"Makoto Hashimoto, Kazuki Ishikawa, Yuri Fukushima, Sarina Shimazu, Mizuha Yabuzaki, Yuka Kamezawa, Takaaki Taguchi, Koji Ichinose","doi":"10.1002/cbic.202500049","DOIUrl":"10.1002/cbic.202500049","url":null,"abstract":"Actinorhodin (ACT) from Streptomyces coelicolor A3(2) is an aromatic polyketide antibiotic with a benzoisochromanequinone (BIQ) skeleton. Although actVI-ORF3 and actVI-ORF4 are not essential for ACT biosynthesis, homologous genes to these are present in the biosynthetic gene clusters of BIQ lactones. In this study, ActVI-ORF3 was identified as a cofactor-independent enzyme with lactonization activity, using ACT as a substrate. ActVI-ORF3 recognized dihydrokalafungin and 8-hydroxykalafafungin, which share the same pyran-ring configuration as ACT, but not nanaomycin A, which has an opposite configuration. In contrast, ActVI-ORF4 functioned as an NAD(P)-dependent oxidoreductase, catalyzing the delactonization of BIQ lactones. Conversion experiments using isotopically labeled compounds revealed that both lactonization and delactonization reactions of these enzymes yielded products in which the carboxyl oxygen at the C1 position was retained. Subsequently, we reexamined the accumulation of ACT-related compounds in the actVI-ORF3 and actVI-ORF-4 disruptants. The results suggested that ACT intermediates are predominantly pooled in the bacteria as (S)-DNPA rather than in lactone-form. The contribution of ActVI-ORF4 to metabolic flux is not significant, and endogenous reductases can convert these intermediates to the dihydro form, which subsequently re-enters the ACT biosynthetic pathway.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500049"},"PeriodicalIF":2.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571776","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

Donor-Acceptor (Perylenethienyl)Ethylenes as Singlet Oxygen-Photogenerating Viral Inhibitors.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-05 DOI: 10.1002/cbic.202401019

Maxim S Krasilnikov, Roman V Mazur, Stepan P Chumakov, Vladislav S Denisov, Efim A Goldenberg, Yan I Nikolaenko, Evgeny A Bersenev, Timofei D Nikitin, Polina S Orinicheva, Vladimir A Brylev, Evgeny L Gulyak, Vladimir A Korshun, Vera A Alferova, Daniil A Gvozdev, Alexey V Ustinov

{"title":"Donor-Acceptor (Perylenethienyl)Ethylenes as Singlet Oxygen-Photogenerating Viral Inhibitors.","authors":"Maxim S Krasilnikov, Roman V Mazur, Stepan P Chumakov, Vladislav S Denisov, Efim A Goldenberg, Yan I Nikolaenko, Evgeny A Bersenev, Timofei D Nikitin, Polina S Orinicheva, Vladimir A Brylev, Evgeny L Gulyak, Vladimir A Korshun, Vera A Alferova, Daniil A Gvozdev, Alexey V Ustinov","doi":"10.1002/cbic.202401019","DOIUrl":"10.1002/cbic.202401019","url":null,"abstract":"The development of broad-spectrum antiviral drugs effective against a wide range of viruses is of significant practical importance. Derivatives of perylene, a pentacyclic aromatic hydrocarbon, demonstrate pronounced antiviral activity. These compounds act primarily as membrane-active singlet oxygen photogenerators, disrupting virions and inhibiting their fusion with the host cell membrane. Modification of the perylene core allows for chemical diversification of antiviral photosensitizers. Additionally, achieving a bathochromic shift of the absorption band is crucial for effective treatment of superficial lesions, as it facilitates deeper tissue penetration of therapeutic light. In this work, donor-acceptor perylenylethylenes and (perylenethienyl)ethylenes were synthesized and evaluated for their spectral properties, singlet oxygen photogeneration, and inhibitory activity against vesicular stomatitis virus (VSV), a representative enveloped virus. Incorporation of a thiophene moiety into the molecule significantly enhanced both the singlet oxygen generation ability and the antiviral activity. These findings provide useful insights into the relationship between the structure, spectral/photochemical properties, and biological activity of perylene-based photosensitizers.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202401019"},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555404","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

Concept and Development of Metal-Framework Nucleic Acids.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-03-05 DOI: 10.1002/cbic.202401067

Li Sun, Xiangyuan Ouyang

{"title":"Concept and Development of Metal-Framework Nucleic Acids.","authors":"Li Sun, Xiangyuan Ouyang","doi":"10.1002/cbic.202401067","DOIUrl":"10.1002/cbic.202401067","url":null,"abstract":"Based on the Watson-Crick base pairing principle, precisely programmable metal-framework nucleic acids (mFNA) have evolved from one-dimensional to three-dimensional nanoscale structures, a technological advancement attributed to progress in DNA nanotechnology. mFNA are a new type of nanomaterial formed by using framework nucleic acids (FNAs) as precise templates to guide the ordered assembly and self-assembly of metal ions, metal salts (such as calcium phosphate, calcium carbonate, etc.), metal nanoclusters, metal nanoparticles, or metal oxide nanoparticles. Compared to traditional FNAs, mFNA not only inherits the powerful programmed self-assembly capabilities of nucleic acids but also incorporates the unique physicochemical properties of inorganic metal nanomaterials. This intersection of organic and inorganic chemistry presents broad application prospects in fields such as biology, chemistry, materials science, and energy science. This review, based on the principles related to FNAs, introduces the concept of mFNA for the first time, aiming to explore the fundamental connections between nanoscale FNAs and metal materials. Additionally, the article focuses on the construction methods and functional characteristics of mFNA. Finally, the current challenges faced by mFNA are reviewed, and their future development is anticipated, providing detailed information for a comprehensive understanding of the research progress in mFNA.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202401067"},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555382","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