ChemBioChem最新文献_第10页

Integration of CRISPR/Cas12a and Toehold-Mediated Strand Displacement for Alternative Conventional miRNA Detection 整合CRISPR/Cas12a和支点介导的链位移用于替代传统miRNA检测。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-16 DOI: 10.1002/cbic.202500932

David Septian Sumanto Marpaung, Ayu Oshin Yap Sinaga, Damayanti Damayanti, Ni Wayan Arya Utari, Harmiansyah, Arthur Karangan, Muh Kusmali

{"title":"Integration of CRISPR/Cas12a and Toehold-Mediated Strand Displacement for Alternative Conventional miRNA Detection","authors":"David Septian Sumanto Marpaung, Ayu Oshin Yap Sinaga, Damayanti Damayanti, Ni Wayan Arya Utari,  Harmiansyah, Arthur Karangan, Muh Kusmali","doi":"10.1002/cbic.202500932","DOIUrl":"10.1002/cbic.202500932","url":null,"abstract":"MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression and serve as powerful biomarkers for cancer and other diseases. Conventional detection methods such as RT-qPCR, Northern blotting, microarrays, and next-generation sequencing provide robust analytical capabilities but remain limited by complexity, cost, and poor suitability for point-of-care diagnostics. CRISPR/Cas12a has emerged as a versatile nucleic acid detection platform with high specificity and sensitivity. However, its intrinsic preference for DNA substrates restricts direct application to miRNA sensing. Early CRISPR/Cas12a-based assays relied on enzymatic amplification, direct RNA-induced activation, or split-component designs, each offering proof-of-concept feasibility but facing trade-offs in sensitivity, workflow complexity, or robustness. Toehold-mediated strand displacement (TSD) provides a powerful alternative by converting miRNA inputs into DNA activators or crRNAs that efficiently trigger Cas12a. This integration enables enzyme-free amplification, programmable logic operations, and enhanced sensitivity, while reducing reliance on multienzyme cascades. This review critically evaluates conventional, enzymatic, direct, and split-based CRISPR/Cas12a strategies and emphasizes emerging TSD-assisted platforms as next-generation solutions for sensitive, specific, and portable miRNA detection.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462357","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 Modified Methyl Transferase Cofactor to Selectively Silence Gene Expression in Escherichia coli 修饰甲基转移酶辅助因子选择性沉默大肠杆菌基因表达。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-16 DOI: 10.1002/cbic.202500737

Oliver J. Irving, Samuel Stone, Robert K. Neely, Tim Albrecht

引用次数: 0

Structure-Activity Relationships of Designed α-Amino Hydroxamic Acids for Affinity Labeling via In Situ Isocyanate Generation. 通过原位异氰酸酯生成亲和标记设计的α-氨基羟肟酸的构效关系。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-13 DOI: 10.1002/cbic.202500939

Kaisei Uegaki, Hayato Ono, Harunori Yoshikawa, Akitomo Kasahara, Kenzo Yamatsugu

引用次数: 0

Enzymatic and Chemical Synthesis for ADP-Ribosylation Using NAD⁺ as Building Blocks: New Concerns in Reaction Discovery and Design. 使用NAD+作为构建块的adp -核糖基化的酶和化学合成：反应发现和设计的新关注点。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-13 DOI: 10.1002/cbic.202500731

Yiran Liu, Yanbo You, Lingjun Li

{"title":"Enzymatic and Chemical Synthesis for ADP-Ribosylation Using NAD+ as Building Blocks: New Concerns in Reaction Discovery and Design.","authors":"Yiran Liu, Yanbo You, Lingjun Li","doi":"10.1002/cbic.202500731","DOIUrl":"https://doi.org/10.1002/cbic.202500731","url":null,"abstract":"Nicotinamide adenine dinucleotide (NAD+), as an endogenous donor for ADP-ribosylation, can modify DNA, RNA, and proteins, thereby participating in the regulation of the functions of these biomacromolecules. NAD+ serves as a reactant in both enzymatic and chemical synthesis. By employing a well-designed reaction process, the synthetic route can be significantly streamlined, enabling the preparation of structurally complex bioactive molecules in a step-saving and highly effective manner. This article reviews the latest research progress in this field. In the field of enzymatic synthesis, a strategy based on the HPF1/PARP1 complex has been developed. Earlier study shows that the recombinant HPF1/PARP1 complex can ADP-ribosylate a variety of substrates in vitro. In the field of chemical synthesis, the focus is on ionic liquid-mediated ADP-ribosylation reactions with controllable α/β configurations of products. These reactions help prepare biologically active ADP-ribosylated (ADPr) peptides from NAD+ and commercially available peptides. In addition, this article also outlines the applications of functional NAD+ derivatives in enzyme activity analysis and inhibitor development and discusses the challenges faced in this field, such as bio-compatible reaction conditions, synthesis for precise structural control, and structure-activity relationships between stereochemistry and biological functions of more ADPr derivatives.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 5","pages":"e202500731"},"PeriodicalIF":2.8,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429836","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

Targeted Protein Degradation by Repurposing Transmembrane E3 Ubiquitin Ligases. 利用跨膜E3泛素连接酶进行靶向蛋白降解。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-13 DOI: 10.1002/cbic.202500870

Jibin Cui, Qian Qu, Man Pan

引用次数: 0

Designed Water Capture in Terpene Synthase Catalysis. 设计萜烯合酶催化的水捕获。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-13 DOI: 10.1002/cbic.70265

Prabhakar L Srivastava, David J Miller, Rudolf K Allemann

{"title":"Designed Water Capture in Terpene Synthase Catalysis.","authors":"Prabhakar L Srivastava, David J Miller, Rudolf K Allemann","doi":"10.1002/cbic.70265","DOIUrl":"10.1002/cbic.70265","url":null,"abstract":"Sesquiterpene synthases catalyse cyclisations and rearrangements of farnesyl diphosphate to produce a diverse array of sesquiterpenes generated by depronotation and/or water capture. However, the precise mechanisms and dynamics controlling the fate of the final carbocationic intermediate are not well understood. In our previous study, we engineered water capture in selina-4(15),7(11)-diene synthase (SpSdS) to produce selin-7(11)-en-4-ol as a major product at pH 6.0 by point mutation (G305E) in the Khelix region. To develop a more generalised protocol for this functional switch in sesquiterpene synthases, we identified and characterised a novel selina-3,7(11)-diene synthase (AsSdS) from Actinacidiphila soli through multiple sequence alignments which naturally contains glutamate at position 305 (E305). Through site-directed mutagenesis, creating variant G221T, we were able to instigate water capture in AsSdS to produce selin-7(11)-en-4-ol. Our findings identified two crucial regions in the active site pocket of selinadiene synthases: G/E305 in Khelix and T/G221 in Hhelix, that have a reproducible effect on product outcome determination. We demonstrate that subtle, yet predictable changes to these residues impact the water capture as well as deprotonation capability of selinadiene synthases and this solvation aspect can be further exploited to engineer other terpene synthases to generate biocatalysts with unique product profiles for diverse applications.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 5","pages":"e70265"},"PeriodicalIF":2.8,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429852","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

Heterocyclic-Fused Squaramides: Anionophores With Antimicrobial Activity. 杂环融合角鲨酰胺：具有抗菌活性的阴离子载体。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-13 DOI: 10.1002/cbic.202500680

Luke Edward Brennan, Chris Samuel Hawes, Kevin Kavanagh, Robert Brian Peter Elmes

引用次数: 0

Human Intestinal Microbiota Composition Shapes Model Polyfluoroalkyl Substance Biotransformation. 人体肠道微生物群组成形成多氟烷基物质生物转化模型。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-13 DOI: 10.1002/cbic.202500905

Sierra T Peskett, Daniel S Grégoire, Amy A Rand

{"title":"Human Intestinal Microbiota Composition Shapes Model Polyfluoroalkyl Substance Biotransformation.","authors":"Sierra T Peskett, Daniel S Grégoire, Amy A Rand","doi":"10.1002/cbic.202500905","DOIUrl":"10.1002/cbic.202500905","url":null,"abstract":"6:2 polyfluoroalkyl phosphate diester (6:2 diPAP) is a prevalent environmental contaminant to which humans are regularly exposed. Environmental microbes can biotransform 6:2 diPAP, and the human gut microbiome can biotransform its congener, 8:2 monoPAP. While the human gut microbiome is highly variable between individuals, potential variability in PAP biotransformation has yet to be assessed. We address this gap using six cohorts (A-F) to examine in vitro biotransformation of 6:2 diPAP by the human gut microbiome. Biotransformation pathways of 6:2 diPAP and their connections to the composition of microbial taxa were assessed using gas chromatography mass spectrometry (GC-MS), liquid chromatography tandem mass spectrometry (LC-MS/MS) and 16S rRNA amplicon sequencing. All cohorts biotransformed 6:2 diPAP but differed in their downstream perfluoroalkyl acid (PFAA) profiles, suggesting diverse biotransformation pathways. Microbial community analysis showed similar alpha diversity across cohorts, while the degree of difference between cohorts varied. The analysis confirmed the initial composition of each cohort's microbial community had a bearing on products stemming from 6:2 diPAP transformation, likely driven by low-abundance microbial taxa. These findings underscore the complexity of microbe-mediated polyfluoroalkyl substance (PFAS) transformation and highlight the need for mechanistic studies that identify the genetic controls governing PFAS transformations in the gut microbiome.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 5","pages":"e202500905"},"PeriodicalIF":2.8,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375377","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

Advancing Targeted Protein Degradation Through Immunoproteasome-Caged N-Degrons 通过免疫蛋白酶体笼化N-Degrons推进靶向蛋白降解。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-12 DOI: 10.1002/cbic.202500715

Jack White, Michael M. Shahid, Mohamed Eldeeb

{"title":"Advancing Targeted Protein Degradation Through Immunoproteasome-Caged N-Degrons","authors":"Jack White, Michael M. Shahid, Mohamed Eldeeb","doi":"10.1002/cbic.202500715","DOIUrl":"10.1002/cbic.202500715","url":null,"abstract":"Proteolysis-targeting chimeras (PROTACs) are a promising therapeutic modality that induces the degradation of proteins of interest, yet continue to be limited by metabolic instability and nonoptimal selectivity. N-degron-based PROTACs, while compact and effective recruiters of N-recognins (E3 ubiquitin ligases), are particularly prone to premature degradation and off-target effects. To address this challenge, Loy et al. introduced a “caged” N-degron PROTAC in which a tetrapeptide-morpholine fragment shields the arginine degron. This sequence is specifically recognized by the immunoproteasome (iCP), an inducible proteasome isoform highly expressed in cancer and inflammatory cells, while absent in most healthy tissues. Upon iCP-mediated cleavage, the degron is unmasked, allowing for the degradation of ABL tyrosine kinase via dasatinib-linked PROTAC activity. This protease-gated strategy integrates endogenous proteolytic specificity into degrader activation, enhancing functional stability while allowing context-dependent specificity. Despite these elegant improvements, some challenges remain regarding cell permeability and disease-dependent iCP expression. Nevertheless, immunoproteasome-gated degron represents a compelling framework for the next generation of N-degron PROTACs. Herein, we highlight these recent findings in the context of the design principles, mechanistic insights, and therapeutic implications of this approach and briefly discuss some key challenges and opportunities for future development.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 5","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429923","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: Biochemical Engineering Perspective on cGAS: From Enzyme Discovery to Potential Industrial Application (ChemBioChem 5/2026) 封面：cGAS的生化工程视角：从酶的发现到潜在的工业应用（ChemBioChem 5/2026）

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-03-12 DOI: 10.1002/cbic.70304

Makram Fataeri, Katrin Rosenthal

引用次数: 0