ChemBioChem最新文献_第8页

Assembly of Branched Chain Amino Acids to Toxic Fibrils may be Related to Pathogenesis of Maple Syrup Urine Disease 支链氨基酸向毒性原纤维的组装可能与枫糖浆尿病的发病机制有关。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-27 DOI: 10.1002/cbic.202500092

Chandra Kanth P, Monisha Patel, Raj Dave, Ankur Singh, Viral Khatri, Aayush Joshi, Sujoy Bandyopadhyay, Manoj Kumar Pandey, Dhiraj Bhatia, Nidhi Gour

{"title":"Assembly of Branched Chain Amino Acids to Toxic Fibrils may be Related to Pathogenesis of Maple Syrup Urine Disease","authors":"Chandra Kanth P, Monisha Patel, Raj Dave, Ankur Singh, Viral Khatri, Aayush Joshi, Sujoy Bandyopadhyay, Manoj Kumar Pandey, Dhiraj Bhatia, Nidhi Gour","doi":"10.1002/cbic.202500092","DOIUrl":"10.1002/cbic.202500092","url":null,"abstract":"Inborn errors of metabolisms (IEMs) are group of diseases caused by mutations in single genes, leading to buildup of metabolites, toxic or disrupt normal cellular function. The etiological relation of metabolic disorders has been uncovered through study of metabolite amyloids. Various metabolites that accumulate in IEMs have been reported to self-assemble into organized structures. These structures exhibit similar physicochemical properties as proteinaceous amyloid fibrils. Our study illustrates the aggregation properties of branched chain amino acids (BCAAs), isoleucine, leucine, and valine that accumulate in maple syrup urine disease (MSUD) to investigate their propensities to assemble into amyloid-like fibrils. The structural morphologies of BCAAs are studied via microscopic techniques. Further, characterization techniques are employed to understand the physicochemical properties of the self-assemblies and their underlying mechanism. The amyloid-like nature of these aggregates is confirmed using thioflavin T and congo red assays. The (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay reveals BCAAs are cytotoxic and significantly decrease cell viability. This study plays a key role in understanding the physicochemical properties of MSUD in the context of amyloid diseases, possibly paving the way for the development of its therapeutic solutions in the future.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 13","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149000","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

Chemical Switching: A Concept Inspired by Strategies from Biocatalysis and Organocatalysis 化学转换：受生物催化和有机催化策略启发的概念。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-26 DOI: 10.1002/cbic.202500220

Torkild Visnes, Kaixin Zhou, Aurino M. Kemas, Dominic Campopiano, Volker M. Lauschke, Maurice Michel

{"title":"Chemical Switching: A Concept Inspired by Strategies from Biocatalysis and Organocatalysis","authors":"Torkild Visnes, Kaixin Zhou, Aurino M. Kemas, Dominic Campopiano, Volker M. Lauschke, Maurice Michel","doi":"10.1002/cbic.202500220","DOIUrl":"10.1002/cbic.202500220","url":null,"abstract":"In this perspective the character of aldehyde functional groups is outlined as central intermediates in DNA repair. As highly reactive entities, aldehydes exist in limited quantities and in contextualized scenarios only and are commonly masked as a Schiff base. Recent advances reveal that principles of organic chemistry can modulate the enzymatic cleavage of Schiff bases, a process termed chemical switching. This approach not only enhances the production of canonical DNA repair products, bolstering cellular function, but also generates novel reaction intermediates, potentially rewiring cellular pathways. However, such rewiring could increase the complexity and toxicity of DNA repair intermediates, influencing therapeutic outcomes. To shape novel classes of therapeutics, an exploitation of these fine-tuned reaction principles requires expertise of enzymologists and scientists skilled in bio- and organocatalysis. Here, the current state of the art is outlined in chemically switching enzymatic function in cells with focus on DNA repair, highlighting challenges of this new type of protein modulation and discussing possible solutions. This paints a picture of the chemical switching concept as an emerging playing field with exciting translational prospects.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 11","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500220","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Tailored Phospho-p53 Library Probes Antibody Specificity and Recognition Limitations 量身定制的phospho-p53文库检测抗体特异性和识别局限性。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-26 DOI: 10.1002/cbic.202500256

Mateusz Hess, Jonathan H. Davies, Sofia Margiola, Sonja Schneider, Thomas Hicks, Nishant Rai, Manuel M. Müller

{"title":"A Tailored Phospho-p53 Library Probes Antibody Specificity and Recognition Limitations","authors":"Mateusz Hess, Jonathan H. Davies, Sofia Margiola, Sonja Schneider, Thomas Hicks, Nishant Rai, Manuel M. Müller","doi":"10.1002/cbic.202500256","DOIUrl":"10.1002/cbic.202500256","url":null,"abstract":"The tumor suppressor protein p53, known as the “guardian of the genome,” is regulated by a complex network of post-translational modifications. Phosphorylations at 7 Ser/Thr residues within the N-terminal transactivation domain 1 (TAD1) play a role in p53 activation, yet their precise mechanisms of action remain elusive due to challenges in accessing well-defined phosphorylated isoforms. To address this limitation, this study harnesses a recently developed approach for the semisynthesis of site-specifically phosphorylated p53 to generate a comprehensive library of singly phosphorylated p53 including all TAD1 sites: Ser6, Ser9, Ser15, Thr18, Ser20, Ser33, and Ser37. The library was then used to probe the specificity of common p53 antibodies in western blot analysis. This study's results confirm the specificity of the target site of most phosphorylation-specific anti-p53 antibodies, but also reveal wide-spread epitope masking by phosphorylation, which has implications for p53 research and diagnostics. This \"designer\" p53 library thus provides a toolkit to study the function of p53 phosphorylation directly and indirectly as a quality control agent for some of the most widely used reagents in the field.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Galactose-Functionalized Gold Nanoparticles Targeting Membrane Transporters for the Glutathione Delivery to Brain Cancer Cells 半乳糖功能化的金纳米颗粒靶向谷胱甘肽向脑癌细胞的膜转运体。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-23 DOI: 10.1002/cbic.202500104

Francesca Milano, Alessia Nito, Annalisa Caputo, Antonio Gaballo, Marco Marradi, Alessandra Quarta, Andrea Ragusa

引用次数: 0

Structural Basis of Regioselective Bromination of Tricyclic Tryptoline by the Tryptophan Halogenase Thal 色氨酸卤化酶区域选择性溴化三环色氨酸的结构基础。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-23 DOI: 10.1002/cbic.202500246

Simon Bork, Caroline Besse, Norbert Sewald, Hartmut H. Niemann

{"title":"Structural Basis of Regioselective Bromination of Tricyclic Tryptoline by the Tryptophan Halogenase Thal","authors":"Simon Bork, Caroline Besse, Norbert Sewald, Hartmut H. Niemann","doi":"10.1002/cbic.202500246","DOIUrl":"10.1002/cbic.202500246","url":null,"abstract":"Flavin-dependent halogenases (FDHs) carry out substrate-specific and regioselective halogenation reactions in the biosynthesis of various halogenated natural compounds. Several FDHs convert non-native substrates in vitro. However, obtaining experimental structures of FDHs with non-native substrates remains challenging, and docking often produces ambiguous results. Hence, there is a lack of data on how non-native substrates bind to FDHs. Here, we show that the tryptophan 6-halogenase Thal efficiently brominates the tricyclic indole derivative tryptoline (1,2,3,4-tetrahydro-β-carboline) with high regioselectivity. The two point mutations G113S and G469S improve regioselectivity even further. A crystal structure reveals how tryptoline binds to the active site of Thal. The halogenated carbons are located close to the catalytic lysine, and the NH of tryptoline's tetrahydropyridine is positioned like the amino group of the native substrate tryptophan. The substrate binding loop of Thal is closed, again resembling the binding of tryptophan. Our work extends the range of non-native substrates accepted by Thal, confirming the versatility of this FDH. Moreover, it is a rare example of an FDH structure in complex with a non-native substrate.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 13","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Cyclized Helix-Loop-Helix Peptide as a Molecular Scaffold for Cell-Membrane Permeable Inhibitors for the Interaction Between Estrogen Receptor α and Coactivator SRC1 环化螺旋-环-螺旋肽作为雌激素受体α与辅激活因子SRC1相互作用的细胞膜渗透性抑制剂的分子支架。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-23 DOI: 10.1002/cbic.202500232

Daisuke Fujiwara, Shunsuke Inaura, Yuna Tanaka, Sayoko Ito-Harashima, Asako Yamaguchi-Nomoto, Masanobu Kawanishi, Takashi Yagi, Ikuhiko Nakase, Ikuo Fujii

引用次数: 0

Hazelnut: Explorations towards the biocatalytic synthesis of its aroma precursor. 榛子：生物催化合成其香气前体的探索。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-22 DOI: 10.1002/cbic.202500192

Mireia Salvadó-Pau, Wolf-Dieter Fessner, Zvjezdana Findrik Blažević, Michael Breuer

{"title":"Hazelnut: Explorations towards the biocatalytic synthesis of its aroma precursor.","authors":"Mireia Salvadó-Pau, Wolf-Dieter Fessner, Zvjezdana Findrik Blažević, Michael Breuer","doi":"10.1002/cbic.202500192","DOIUrl":"https://doi.org/10.1002/cbic.202500192","url":null,"abstract":"Biocatalysis has gained significant industrial interest due to its controlled stereoselectivity and use of mild process conditions. Here we propose a biosynthetic route for the synthesis of filbertone (5-methyl-2-hepten-4-one, 1), which is the principal flavour compound of hazelnut. The enantiomeric purity of the industrially synthesized compound is defined, contrary to the natural aroma, which varies according to the source of the nut extraction conditions and treatments. The novel synthetic pathway for a hazelnut aroma precursor proposed here consists of a multi-enzyme cascade, which starts from the two amino acids D-Ile and L-Thr that are individually converted by enzyme catalysts, i.e., D-amino acid oxidase and threonine deaminase, followed by C-C ligation of the obtained products allowing a potentially sustainable production of the natural aroma. The most critical step is C-C ligation that uses two carbonyl compounds as starting material. This step is catalysed by a regioselective transketolase (TK) that originates from Geobacillus stearothermophilus. Our approach holds promise for an industrial production of natural hazelnut aroma precursor, addressing the growing demand in the aroma industry for synthesis methods that sustain the regulatory claims for natural compounds.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500192"},"PeriodicalIF":2.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118435","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

Designing an Entactin-Inspired Short Bioactive Hydrogel as Biofunctional Scaffold 一种受肠动蛋白启发的短生物活性水凝胶作为生物功能支架的设计。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-22 DOI: 10.1002/cbic.202500260

Shambhavi Kashyap, Sweta Mohanty, Sourav Sen, Sangita Roy

{"title":"Designing an Entactin-Inspired Short Bioactive Hydrogel as Biofunctional Scaffold","authors":"Shambhavi Kashyap, Sweta Mohanty, Sourav Sen, Sangita Roy","doi":"10.1002/cbic.202500260","DOIUrl":"10.1002/cbic.202500260","url":null,"abstract":"Self-assembled peptide hydrogels developed from bioactive domains of extracellular matrix (ECM) have shown great capabilities to mimic the structural and functional aspects of ECM. In this direction, the self-assembling potential of a minimalist bioactive sequence (YWTD) derived from one of the essential bridging proteins of ECM, i.e., entactin, is explored. However, at physiological pH, the negative charge of the aspartate residue induces strong intermolecular repulsion that prevents the self-assembly of the peptide monomers. Interestingly, the peptide forms self-supporting hydrogels at a slightly acidic pH, i.e., pH 6.2, through surface charge neutralization, thereby minimizing the repulsive interaction. Since it is aimed to explore its use in controlling cellular adhesion and proliferation, the buffering capacity of the media is utilized to adjust the pH of the gel to physiological levels. To the best of our knowledge, this is the first report on self-assembly of a novel bioactive sequence derived from the G3 domain of entactin protein. These hydrogels self-assembled at physiological pH display a nanofibrous structure with tuneable mechanical stiffness, which are biocompatible toward fibroblast cells. An improved cellular adhesion and proliferation are evident within this novel matrix, thus proving it as a suitable biomaterial with future potential in the field of biomedicine.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126331","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

Engineering Nicotinamide Adenine Dinucleotide Oxidase for Regeneration of Oxidized Non-natural Cofactor. 工程NADH氧化酶再生氧化非天然辅助因子。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-22 DOI: 10.1002/cbic.202500254

Yeyu Liu, Xueying Wang, Yinghan Hu, Yanzhe Huang, Lingyun Zhang, Haizhao Xue, Yongjin J Zhou, Zongbao K Zhao

{"title":"Engineering Nicotinamide Adenine Dinucleotide Oxidase for Regeneration of Oxidized Non-natural Cofactor.","authors":"Yeyu Liu, Xueying Wang, Yinghan Hu, Yanzhe Huang, Lingyun Zhang, Haizhao Xue, Yongjin J Zhou, Zongbao K Zhao","doi":"10.1002/cbic.202500254","DOIUrl":"10.1002/cbic.202500254","url":null,"abstract":"Nicotinamide adenine dinucleotide (NAD+) and its reduced form NADH are universal redox cofactors, and thus manipulating NAD(H) supply often leads to unpredictable outcome because of metabolic crosstalk. To overcome intrinsic limitations associated to natural cofactors, this study previously introduces nicotinamide cytosine dinucleotide (NCD+) as a non-natural cofactor for redox biochemistry. While several enzymes have been devised to generate NCDH as driving force at the expense of cheap chemicals for reductive metabolic reactions, it remains inaccessible to generate NCD+ for oxidative reactions. In this study, it engineers an H2O-forming NADH oxidase (EfNOX) from Enterococcus faecalis to favor NCDH. Compared to the wild-type enzyme, the best mutant NADH oxidase (NOX)-KRGT oxidizes NCDH with 14- and 107-fold higher catalytic efficiency and selectivity, respectively. Docking analysis shows that those mutations acquired a narrower cofactor binding cavity and positively charged environment contributing to the preference toward NCDH. Coupling NOX mutants with NCD-favoring phosphite dehydrogenase mutant enables Escherichia coli BW14329 to utilize phosphite as sole phosphorus source for growth. This work provides a traceless and effective tool to convert NCDH into NCD+, which should greatly expand our capacity in developing NCD-linked redox subsystems and further facilitate the implementation of non-natural cofactors in chemical biology and synthetic biology.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500254"},"PeriodicalIF":2.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118434","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

Development of Thiol-Labile α-Amino Protecting Groups for Efficient Solid-Phase Peptide Synthesis. 高效固相合成巯基α-氨基保护基团的研究。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-21 DOI: 10.1002/cbic.202500236

Hongjun Li, Yifei Zhou, Linhai Yan, Xiang Zhu, Xinrui Tian, Zhen Xi, Chuanzheng Zhou

{"title":"Development of Thiol-Labile α-Amino Protecting Groups for Efficient Solid-Phase Peptide Synthesis.","authors":"Hongjun Li, Yifei Zhou, Linhai Yan, Xiang Zhu, Xinrui Tian, Zhen Xi, Chuanzheng Zhou","doi":"10.1002/cbic.202500236","DOIUrl":"https://doi.org/10.1002/cbic.202500236","url":null,"abstract":"Recently, a thiol-labile α-amino-protecting group, 2,4-dinitro-6-phenyl-benzenesulfenyl (DNPBS), is introduced for solid-phase peptide synthesis (SPPS). DNPBS-SPPS effectively mitigates major side reactions-such as aspartimide formation and α-C racemization-that commonly occur in conventional Fmoc-SPPS. However, N-DNPBS-protected histidine is unstable during the base-catalyzed peptide bond coupling, leading to histidine redundant insertion byproducts (Nat. Commun. 2023, 14, 5324). In this study, modifications to the nitrobenzenesulfenyl protecting group are explored and their impact on chemical stability and thiol-mediated deprotection kinetics are systematically evaluated. It is found that introducing a C6 substituent and replacing the phenyl group with a pyridine ring significantly modulate both stability and thiol susceptibility. Notably, 3-nitro-2-pyridinesulfenyl (Npys) outperforms DNPBS in SPPS. N-Npys-protected histidine exhibits markedly greater stability than its N-DNPBS-protected counterpart, effectively preventing histidine redundant insertion byproducts commonly observed in DNPBS-SPPS. This study provides valuable insights into optimizing nitrobenzenesulfenyl-based protecting groups for more efficient SPPS.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500236"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109067","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