ChemBioChem最新文献_第5页

Front Cover: Photoactivatable Alkyne Tag for Photolabeling Biomolecules in Living Cells (ChemBioChem 17/2025) 封面：用于光标记活细胞中生物分子的光活化炔标签（ChemBioChem 17/2025）

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-17 DOI: 10.1002/cbic.70018

Yuki Umeda, Hao Zhu, Satoshi Yamaguchi, Sho Nakamura, Masato Takada, Shin Izuta, Akimitsu Okamoto

引用次数: 0

Enantiocomplementary Bioreduction of Flexible Ring N-(3-Oxobutyl)Heterocycles Providing Enantiopure Chiral Fragments for Drug Discovery 柔性环N-（3-氧丁基）杂环的对映互补生物还原为药物发现提供对映不纯手性片段。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-17 DOI: 10.1002/cbic.202500601

Máté Gergő Honvári, Levente András Mócza, Bence Attila Kucsinka, Pál Csuka, Viktória Bódai, Diana Maria Scrob, László Poppe, Gábor Hornyánszky

{"title":"Enantiocomplementary Bioreduction of Flexible Ring N-(3-Oxobutyl)Heterocycles Providing Enantiopure Chiral Fragments for Drug Discovery","authors":"Máté Gergő Honvári, Levente András Mócza, Bence Attila Kucsinka, Pál Csuka, Viktória Bódai, Diana Maria Scrob, László Poppe, Gábor Hornyánszky","doi":"10.1002/cbic.202500601","DOIUrl":"10.1002/cbic.202500601","url":null,"abstract":"In this study, the bioreduction of prochiral N-(3-oxobutyl)heterocycles comprising various (partially) saturated, flexible rings is explored using microbial whole-cell ketoreductases such as wild-type yeast strains including baker's yeast (Saccharomyces cerevisiae) and Escherichia coli cells expressing two enantiocomplementary recombinant alcohol dehydrogenases. Initially, four wild-type yeast strains are screened for ketoreductase activity on a series of nine flexible N-heterocycles with prochiral carbonyl group in the N-(3-oxobutyl) sidechain. The yeast strains resulted in the corresponding (S)-alcohols with a low to moderate conversions. Using recombinant alcohol dehydrogenase whole-cell preparations as biocatalysts ((S)-selective ADH from Rhodococcus aetherivorans (RaADH) and (R)-selective ADH from Lactobacillus kefir (LkADH)) resulted in higher conversions in most cases, while maintaining the full enantiotopic selectivity. Usually, the preparative-scale bioreductions showed comparable or even higher conversions than those observed in the small-scale screening reactions, resulting in virtually enantiopure (S)- and (R)-alcohols (ee > 99%), which are promising chiral fragments with a high degree of drug-likeness. Docking studies confirmed the absolute configuration of the forming (S)- and (R)-alcohols.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079159","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

Effects on LuxR-Regulated Bioluminescence of Cyclodextrin-Acyl-L-Homoserine Lactone Hybrids 环糊精-酰基- l-高丝氨酸内酯杂合体对luxr调控生物发光的影响。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-17 DOI: 10.1002/cbic.202500525

Nicolas Tinet, David Lesur, Yves Queneau, Laurent Soulère, Florence Djedaini-Pilard, Véronique Bonnet

{"title":"Effects on LuxR-Regulated Bioluminescence of Cyclodextrin-Acyl-L-Homoserine Lactone Hybrids","authors":"Nicolas Tinet, David Lesur, Yves Queneau, Laurent Soulère, Florence Djedaini-Pilard, Véronique Bonnet","doi":"10.1002/cbic.202500525","DOIUrl":"10.1002/cbic.202500525","url":null,"abstract":"In this work, acyl homoserine lactones (AHLs) are grafted, the most studied signaling molecules in many Gram-negative bacteria, onto cyclodextrins (CDs) by copper-catalyzed azide–alkyne cycloaddition “click” coupling between alkynyl-AHLs and 6-azido-CDs derived from α- and β-CD, native or methylated. Attaching biomolecules onto a CD scaffold is a known strategy to enhance their properties, but designing CD-AHL conjugates has never been reported. These molecules were fully characterized by NMR and high-resolution mass spectrometry, and the study of their solubility and conformation reveals significant conformational changes due to the presence of the AHL appendage on the CD structure. One of the hybrids (per-AHL-β-CD, 9B) exhibits higher solubility in water than AHL and β-CD alone. The new CD-AHLs conjugates are found to modulate bioluminescence in a quorum Sensing LuxR-regulated light-producing bacterial model, with significant variations depending on the structure. The per-AHL-β-CD, 9B, is found to be the most active compound in the series.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079152","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

Front Cover: Development and Recent Advances in SLIPT-PM: A Chemogenetic Platform for Manipulating Signaling at the Plasma Membrane (ChemBioChem 16/2025) 封面：slip - pm的发展和最新进展：一个操纵质膜信号传导的化学发生平台（ChemBioChem 16/2025）

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-13 DOI: 10.1002/cbic.70016

Shuya Ohira, Akinobu Nakamura, Kenta Terai, Shinya Tsukiji

引用次数: 0

Cover Feature: Engineering Nicotinamide Adenine Dinucleotide Oxidase for Regeneration of Oxidized Non-natural Cofactor (ChemBioChem 16/2025) 封面特写：用于氧化非天然辅因子再生的工程烟酰胺腺嘌呤二核苷酸氧化酶（ChemBioChem 16/2025）

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-13 DOI: 10.1002/cbic.70015

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

引用次数: 0

A Photocaged N-Phosphonopiperidinone as a Selective Photo-Cleavable DPP8/9 Inhibitor 光笼化n -膦吡啶酮作为选择性光裂解DPP8/9抑制剂

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-12 DOI: 10.1002/cbic.202500558

Leonard Sewald, Niko Molke, Werner W. A. Tabak, Anette Haak, Maja Najdzion, Ruth Geiss-Friedlander, Doris Hellerschmied, Robert Huber, Markus Kaiser

{"title":"A Photocaged N-Phosphonopiperidinone as a Selective Photo-Cleavable DPP8/9 Inhibitor","authors":"Leonard Sewald, Niko Molke, Werner W. A. Tabak, Anette Haak, Maja Najdzion, Ruth Geiss-Friedlander, Doris Hellerschmied, Robert Huber, Markus Kaiser","doi":"10.1002/cbic.202500558","DOIUrl":"10.1002/cbic.202500558","url":null,"abstract":"The strategic introduction of photocages into chemical probes represents a powerful approach to generate spatiotemporally controlled tools with promising applications in chemical biology and drug discovery. This approach is particularly useful for inhibitors of proteins with cell-type-dependent functions, as they enable, via light-triggered selection, the study of their function in selected cells within multicellular organisms. The intracellular dipeptidyl peptidases 8 and 9 (DPP8/9) are serine hydrolases that act in a cell type-dependent fashion, in diverse biological processes such as inflammation and tumorigenesis. So far, no photocaged inhibitors for DPP8/9 are available, thus hampering their systematic investigations in biomedical research model systems such as mice. Herein, the development of a green light-cleavable, BODIPY-photocaged N-phosphono-piperidone-based DPP8/9 inhibitor is presented. This covalent-acting inhibitor is characterized by its photolysis properties, including a demonstration of its low phototoxicity, as well as potency and selectivity, in biochemical, biological, and, as an extension to these traditional validation approaches, chemical proteomics assays. These studies not only reveal the suitability of the developed photocages for cellular applications, as a prerequisite for their application in multicellular organisms, but also highlight the benefit of chemical proteomics workflows such as activity-based protein profiling for characterizing proteome-wide potencies and selectivities of photocaged compounds.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051406","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

Indomethacin-Naphthalimide-Based AIEgen for Illuminating Golgi Apparatus 吲哚美辛-萘酰亚胺基照明高尔基装置光源。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-12 DOI: 10.1002/cbic.202500457

Phanindra Kumar, Tripti Mishra, Sanyam, Asima Sahu, Anirban Mondal, Sudipta Basu

{"title":"Indomethacin-Naphthalimide-Based AIEgen for Illuminating Golgi Apparatus","authors":"Phanindra Kumar, Tripti Mishra,  Sanyam, Asima Sahu, Anirban Mondal, Sudipta Basu","doi":"10.1002/cbic.202500457","DOIUrl":"10.1002/cbic.202500457","url":null,"abstract":"Golgi apparatus (GA) is a complex organelle controlling subcellular protein modifications, sorting, and transport. Dysregulation in GA leads to cancer development and metastasis. Consequently, development of small molecule fluorophores for illuminating GA in cancer cells remains a major challenge. To address this, herein, a small molecule library of four aggregation-induced emissive probes (AIEgens) is designed and synthesized, having (a) indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) for GA homing; (b) 1,8-naphthalimide-N,N′-disubstituted aniline as AIE inducer; and (c) amide/ester linkage between NSAID and AIE inducer. All the library members exhibited excellent AIE property in THF/water binary solvent systems through self-assembly in water. Interestingly, one of the library members (compound 13), consisting of napthalimide-N,N′-dimethyl aniline as AIE inducer and amide linkage, efficiently homes into the GA of HCT-116 colon cancer cells within 30 min and self-assembled into 2D nanoscale materials, as shown by scanning electron and atomic force microscopy and confirmed by molecular dynamics (MD) simulations. Moreover, quantum mechanical calculations revealed intramolecular charge transfer (CT) between N,N′-dimethyl aniline (donor) and naphthalimide (acceptor) as the underlying mechanism of the photophysical properties of compound 13. This novel AIEgen can serve as a chemical biology tool to visualize GA in cancer cells for next-generation cancer therapeutics.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051481","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

Two-Color Timestamping of Gene Expression with a Chemigenetic Reporter System 利用化学遗传报告系统研究基因表达的双色时间戳。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-12 DOI: 10.1002/cbic.202500494

Henriette Lämmermann, Jade Nguyen, Juan F. Tamez-Fernández, Fabien Kuttler, Julien Bortoli Chapalay, Marc Chambon, Gerardo Turcatti, Pablo Rivera-Fuentes

引用次数: 0

Characterization of the N-Hydroxylating Monooxygenase TheA from Thermocrispum agreste Reveals a Broad Substrate Spectrum 热薯中n -羟基化单加氧酶TheA的表征揭示了其广泛的底物谱。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-11 DOI: 10.1002/cbic.202500574

Artur Maier, Daniel Fast, Dmytro Sakalo, Lindelo Mguni, Dirk Tischler

{"title":"Characterization of the N-Hydroxylating Monooxygenase TheA from Thermocrispum agreste Reveals a Broad Substrate Spectrum","authors":"Artur Maier, Daniel Fast, Dmytro Sakalo, Lindelo Mguni, Dirk Tischler","doi":"10.1002/cbic.202500574","DOIUrl":"10.1002/cbic.202500574","url":null,"abstract":"The N-hydroxylating monooxygenase (NMO) TheA from Thermocrispum agreste catalyzes the N-hydroxylation step of l-ornithine, which is the first step in the thermochelin siderophore biosynthesis. Characterization of this enzyme revealed a significant thermostability up to 50 °C and activity with the non-native substrate d-ornithine with kinetic parameters (Km = 4.06 ± 0.31 mM, kcat = 0.057 ± 0.001 s−1, and kcat/Km = 0.007 s−1 mM−1) and a coupling rate of 81%. The enzyme is applied in a one-pot reaction with a formate dehydrogenase variant for NADPH regeneration and catalase for H2O2 detoxification. Optimization of the reaction conditions resulted in activity with various non-native substrates such as d-ornithine, l-lysine, S-(2-aminoethyl)-l-cysteine, and l-arginine. Products are confirmed through LC-MS/MS, and mutagenesis experiments gave insight on the potentially underlying mechanisms. This work identifies a thermotolerant NMO that is suitable for application and as a starting point for enzyme engineering.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500574","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032487","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 Nucleotide-Derived Fluorophore for Visualizing G-Quadruplex Assembly and Introduction of Cation-Regulated Activity into the Thrombin Binding Aptamer 用于可视化g -四重体组装的核苷酸衍生荧光团和引入凝血酶结合适体的阳离子调节活性。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-09-11 DOI: 10.1002/cbic.202500416

Rugiya Alieva, Svetlana Sokolova, Ilya Oleynikov, Roman Novikov, Timofei Zatsepin, Andrey Aralov, Elena Zavyalova

{"title":"A Nucleotide-Derived Fluorophore for Visualizing G-Quadruplex Assembly and Introduction of Cation-Regulated Activity into the Thrombin Binding Aptamer","authors":"Rugiya Alieva, Svetlana Sokolova, Ilya Oleynikov, Roman Novikov, Timofei Zatsepin, Andrey Aralov, Elena Zavyalova","doi":"10.1002/cbic.202500416","DOIUrl":"10.1002/cbic.202500416","url":null,"abstract":"Nucleic acid aptamers are artificial recognition elements with great potential in biotechnology. For their effective integration into nanodevices, rational strategies for optimizing aptamer affinity and regulating activity are essential. Artificial nucleotide analogs offer versatile tools for both fundamental and applied research in the aptamer field. Herein, the affinity of a thrombin-binding aptamer is increased tenfold through a single nucleotide modification with 7,8-dihydro-8-oxo-1, N6-ethenoadenine (oxo-εA) introduced at either the 4th or 13th position. Normally, thymines in these positions form a T:T base pair, which is broken during the thrombin binding. A double oxo-εA modification at both the 4th and 13th positions resulted in Ag+-dependence of aptamer activity. Ag+ ions formed a noncanonical oxo-εA:Ag+2:oxo-εA pair, mimicking the T:T pair found in the unmodified aptamer, which is a crucial part of the thrombin recognition interface. The intrinsic fluorescence of oxo-εA is used to investigate conformational rearrangements in the loops during G-quadruplex (GQ) folding. The rapid kinetics of aptamer folding are captured using a stopped-flow fluorimeter. The dissociation constants are estimated for the aptamer complexes with K+, Na+, and Ag+, revealing the tiny influence of the modifications on GQ folding.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032451","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