IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-25 DOI: 10.1002/cbic.202400712

Thaleia Sakoleva, Florian Vesenmaier, Lena Koch, Jarne E. Schunke, Kay D. Novak, Sascha Grobe, Mark Dörr, Uwe T. Bornscheuer, Thomas Bayer

{"title":"Biosensor-Guided Engineering of a Baeyer-Villiger Monooxygenase for Aliphatic Ester Production","authors":"Thaleia Sakoleva, Florian Vesenmaier, Lena Koch, Jarne E. Schunke, Kay D. Novak, Sascha Grobe, Mark Dörr, Uwe T. Bornscheuer, Thomas Bayer","doi":"10.1002/cbic.202400712","DOIUrl":"https://doi.org/10.1002/cbic.202400712","url":null,"abstract":"Esters are valuable aroma compounds and can be produced enzymatically by Baeyer-Villiger monooxygenases (BVMOs) from (aliphatic) ketone precursors. However, a genetically encoded biosensor system for the assessment of BVMO activity and the detection of reaction products is missing. In this work, we assembled a synthetic enzyme cascade – featuring an esterase, an alcohol dehydrogenase, and LuxAB – in the heterologous host Escherichia coli. Target esters are produced by a BVMO, subsequently cleaved, and the corresponding alcohol oxidized through the artificial pathway. Ultimately, aldehyde products are detected in vivo by LuxAB, a luciferase from Photorhabdus luminescens that emits bioluminescence upon the oxidation of aldehydes to the corresponding carboxylates. This biosensor system greatly accelerated the screening and selection of active BVMO variants from a focused library, omitting commonly used low-throughput chromatographic analysis. Engineered enzymes accepted linear aliphatic ketones such as 2-undecanone and 2-dodecanone and exhibited improved ester formation.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317796","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

Cavity-Based Discovery of New Fatty Acid Photodecarboxylases. 基于空腔的新型脂肪酸光脱羧酶的发现。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-24 DOI: 10.1002/cbic.202400631

Stefan Simić, Marco Cespugli, Michael C Hetmann, Ursula Kahler, Valentina Jurkaš, Marikagiusy Di Giacomo, Maria Elena Russo, Antonio Marzocchella, Christian C Gruber, Bettina M Nestl, Christoph K Winkler, Wolfgang Kroutil

{"title":"Cavity-Based Discovery of New Fatty Acid Photodecarboxylases.","authors":"Stefan Simić, Marco Cespugli, Michael C Hetmann, Ursula Kahler, Valentina Jurkaš, Marikagiusy Di Giacomo, Maria Elena Russo, Antonio Marzocchella, Christian C Gruber, Bettina M Nestl, Christoph K Winkler, Wolfgang Kroutil","doi":"10.1002/cbic.202400631","DOIUrl":"https://doi.org/10.1002/cbic.202400631","url":null,"abstract":"Light-dependent fatty acid photodecarboxylases (FAPs) hold significant potential for biotechnology, due to their capability to produce alka(e)nes directly from the corresponding (un)saturated natural fatty acids requiring light as the only reagent. This study expands the family of FAPs through cavity-based enzyme discovery methods. Thirty enzyme candidates with potential photodecarboxylation activity were identified by matching the cavities of four related template structures against the Protein Data Bank's flavoproteins, a library of proteins identified via the Foldseek Search Server, and homology models of sequences resulting from BLAST. Subsequent docking experiments narrowed this library to ten promising enzymes, which were expressed and assessed in vitro, identifying four photodecarboxylases. Out of these enzymes, the GMC oxidoreductase from Coccomyxa sp. Obi (CoFAP) was characterized in detail, which revealed high activity in the decarboxylation reactions of palmitic acid and octanoic acid and a broad pH tolerance (pH 6.5-9.5).","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306688","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

Optogenetic Tools for Regulating RNA Metabolism and Functions. 调节 RNA 代谢和功能的光遗传学工具。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-24 DOI: 10.1002/cbic.202400615

Ru Zheng, Zhaolin Xue, Mingxu You

引用次数: 0

Chemical tools for probing the Ub/Ubl conjugation cascades. 探测 Ub/Ubl 共轭级联的化学工具。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-23 DOI: 10.1002/cbic.202400659

Tomasz Kochanczyk, Michael Fishman, Christopher D Lima

{"title":"Chemical tools for probing the Ub/Ubl conjugation cascades.","authors":"Tomasz Kochanczyk, Michael Fishman, Christopher D Lima","doi":"10.1002/cbic.202400659","DOIUrl":"https://doi.org/10.1002/cbic.202400659","url":null,"abstract":"Conjugation of ubiquitin (Ub) and structurally related ubiquitin-like proteins (Ubl's), essential for many cellular processes, employs muti-step reactions orchestrated by specific E1, E2 and E3 enzymes. The E1 enzyme activates the Ub/Ubl C-terminus in an ATP-dependent process that results in the formation of a thioester linkage with the E1 active site cysteine. The thioester activated Ub/Ubl is transferred to the active site of an E2 enzyme which then interacts with an E3 enzyme to promote conjugation to the target substrate. The E1-E2-E3 enzymatic cascades utilize labile intermediates, extensive conformational changes, and vast combinatorial diversity of short-lived protein-protein complexes to conjugate Ub/Ubl to various substrates in a regulated manner. In this review, we discuss various chemical tools and methods used to study the consecutive steps of Ub/Ubl activation and conjugation, which are often too elusive for direct studies. We focus on methods developed to probe enzymatic activities and capture and characterize stable mimics of the transient intermediates and transition states thereby providing insights into fundamental mechanisms in the Ub/Ubl conjugation pathways.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306689","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

Amyloid-like Aggregation Propensities of Metabolites - Homogentisic acid, N-Acetyl aspartic acid and Isovaleric acid. 代谢物--高戊二酸、N-乙酰天冬氨酸和异戊二酸的淀粉样凝集倾向。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-23 DOI: 10.1002/cbic.202400109

Raj Dave, Ankita Jaiswal, Anam Naseer, Ankita Tripathi, Monisha Patel, Sandeep Verma, Kshatresh Dutta Dubey, Aamir Nazir, Nidhi Gour, Neeraja Revie

{"title":"Amyloid-like Aggregation Propensities of Metabolites - Homogentisic acid, N-Acetyl aspartic acid and Isovaleric acid.","authors":"Raj Dave, Ankita Jaiswal, Anam Naseer, Ankita Tripathi, Monisha Patel, Sandeep Verma, Kshatresh Dutta Dubey, Aamir Nazir, Nidhi Gour, Neeraja Revie","doi":"10.1002/cbic.202400109","DOIUrl":"https://doi.org/10.1002/cbic.202400109","url":null,"abstract":"The transformation of metabolites into amyloidogenic aggregates represent an intriguing dimension in the pathophysiology of metabolic disorders, including alkaptonuria, canavan disease, and isovaleric acidemia. Central to this phenomenon are the metabolites homogentisic acid (HA), N-acetyl aspartic acid (NAA), and isovaleric acid (IVA), which we found, weave an intricate network of self-assembled structures. Leveraging an array of microscopy techniques, we traced the morphological behavior of these assemblies that exhibit concentration and time-dependent morphological transitions from isolated globules to clustered aggregates. MD simulation studies suggest significant role of hydrogen bonding interactions in the aggregation process. While displaying strong amyloidogenic propensity in solution, these aged aggregates were significantly cytotoxic to mouse neural N2a cell lines. In vivo effect in Caenorhabditis elegans (C. elegans) nematode further validated cytotoxicity of aggregates. Our findings provide fresh insights to amyloidogenic nature of HA, NAA, and IVA aggregates and their possible role in associated metabolic disorders such as alkaptonuria, canavan disease and isovaleric acidemia.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306687","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

Site-specific modification of native IgGs with flexible drug-load. 以灵活的药物负载对原生 IgG 进行特定位点修饰。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-21 DOI: 10.1002/cbic.202400511

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

{"title":"Site-specific modification of native IgGs with flexible drug-load.","authors":"Jöri E Wehrmüller, Julia C Frei, Torsten Hechler, Michael Kulke, Andreas Pahl, Martin Béhé, Roger Schibli, Philipp R Spycher","doi":"10.1002/cbic.202400511","DOIUrl":"https://doi.org/10.1002/cbic.202400511","url":null,"abstract":"Homogeneous, site-specifically conjugated antibodies have shown to result in antibody-drug conjugates (ADCs) with improved efficacy and tolerability compared to stochastically conjugated ADCs. However, precisely controlling the drug-load as well as attaching multiple payload moieties on the antibody remains challenging. Here, we demonstrate the simple and direct modification of native IgG-antibodies at the residue glutamine 295 (Q295) without the need for any protein engineering at flexible drug-to-antibody ratios of one or multiple payloads. The conjugation is enabled through short, positively charged lysine containing peptides and native, commercially available microbial transglutaminase. In proof-of-concept studies, HER2-targeting ADCs based on trastuzumab were generated with drug-to-antibody ratios (DARs) of 2 and 4 of the same or different payloads using orthogonal conjugation chemistries. Quantitative biodistribution studies performed with 111In-radiolabeled conjugates showed high tumour uptake and low accumulation of radioactivity in non-targeted tissues. A single dose study of trastuzumab conjugated to the highly potent payload α-Amanitin demonstrated complete and long-lasting tumour remissions and was well-tolerated at all dose levels tested.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277531","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

Synthesis and antiproliferative activity of cisplatin-3-chloropiperidine conjugates 顺铂-3-氯哌啶共轭物的合成与抗增殖活性

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-20 DOI: 10.1002/cbic.202400519

Richard Göttlich, Mats Georg, Anton A. Legin, Michaela Hejl, Michael A. Jakupec, Jonathan Becker

{"title":"Synthesis and antiproliferative activity of cisplatin-3-chloropiperidine conjugates","authors":"Richard Göttlich, Mats Georg, Anton A. Legin, Michaela Hejl, Michael A. Jakupec, Jonathan Becker","doi":"10.1002/cbic.202400519","DOIUrl":"https://doi.org/10.1002/cbic.202400519","url":null,"abstract":"We report the synthesis and characterization of two novel cisplatin- alkylating agents conjugates. Combining a platinum based cytostatic agent with a sterically demanding alkylating agent could potentially induce further DNA damage, block cell repair mechanisms and keep the substrate active against resistant tumor cell lines. The 3-chloropiperidines utilized as ligands in this work are cyclic representatives of the N-mustard family and were not able to coordinate platinum on their own. The introduction of a second coordination site, in form of a pyridine moiety, led to the isolation of the desired conjugates. They were characterized with HRMS, CHN-analyses and XRD. We concluded this work by examining the cytotoxicity of the ligands and the obtained complexes with MTT assays in human cancer cell lines. While the ligands showed hardly any activity, the novel conjugates both displayed a high antiproliferative and cytotoxic potency in a panel of three cell lines. Moreover, both complexes were able to largely circumvent the acquired cisplatin resistance of A2780cisR ovarian cancer cells, both in the MTT assay and a flow-cytometric apoptosis assay.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256858","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 Expressed RNA Strand Displacement for Cellular Manipulation. 用于细胞操作的基因表达 RNA 链置换。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-20 DOI: 10.1002/cbic.202400669

Chao-Qun Wu, Hui-Ye Feng, Yan Liu, Liang Xu

引用次数: 0

Discovery of 18F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype-3 Receptor. 发现 18F 标记的 AZD5213 衍生物作为靶向组胺亚型-3 受体的新型正电子发射断层扫描 (PET) 放射配体。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-20 DOI: 10.1002/cbic.202400655

Zhendong Song, Yinlong Li, Kenneth Dahl, Ahmad Chaudhary, Zhenkun Sun, Xin Zhou, Jiahui Chen, Yabiao Gao, Jian Rong, Chunyu Zhao, Jimmy S Patel, Lee Collier, Chongzhao Ran, Chuangyan Zhai, Linqi Zhang, Ahmed Haider, Kim S Mühlfenzl, Hongjie Yuan, Charles S Elmore, Magnus Schou, Steven Liang

{"title":"Discovery of 18F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype-3 Receptor.","authors":"Zhendong Song, Yinlong Li, Kenneth Dahl, Ahmad Chaudhary, Zhenkun Sun, Xin Zhou, Jiahui Chen, Yabiao Gao, Jian Rong, Chunyu Zhao, Jimmy S Patel, Lee Collier, Chongzhao Ran, Chuangyan Zhai, Linqi Zhang, Ahmed Haider, Kim S Mühlfenzl, Hongjie Yuan, Charles S Elmore, Magnus Schou, Steven Liang","doi":"10.1002/cbic.202400655","DOIUrl":"https://doi.org/10.1002/cbic.202400655","url":null,"abstract":"The histamine subtype 3 (H3) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H3 receptor. In this study, we synthesized and evaluated the binding effects of [18F]H3-2404 and [18F]H3-2405 by modifying the structure of AZD5213, a selective H3 antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non-specific distribution in rodent brain. Although these data suggest that [18F]H3-2404 and [18F]H3-2405 are unsuitable as PET tracers for brain imaging of the H3 receptor, this study provides a valuable attempt for optimizing 18F labeled radiotracers based on AZD5213.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277529","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

SnO2 encapsulated in alginate matrix: Evaluation and optimization of bioinspired nanoadsorbents for azo dye removal 藻酸盐基质中封装的二氧化硒：评估和优化用于去除偶氮染料的生物纳米吸附剂

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-19 DOI: 10.1002/cbic.202400567

Shikha Jyoti Borah, Ravinder Kumar, Praduman Prasad Singh, Vinod Kumar

{"title":"SnO2 encapsulated in alginate matrix: Evaluation and optimization of bioinspired nanoadsorbents for azo dye removal","authors":"Shikha Jyoti Borah, Ravinder Kumar, Praduman Prasad Singh, Vinod Kumar","doi":"10.1002/cbic.202400567","DOIUrl":"https://doi.org/10.1002/cbic.202400567","url":null,"abstract":"Synthesized SnO2 NPs demonstrate potential capacity to adsorb toxic azo dye. Powder X-ray diffraction and SEM imaging confirmed the rutile phase and spherical morphology of SnO2 NPs. Average particle size has been confirmed to be approximately 3 nm through TEM analysis. Adsorption capacity is attributed to the high surface and presence of oxygen vacancy confirmed through BET and XPS, respectively. To mitigate the leaching of NPs in treated water, the encapsulation of NPs in sodium alginate (SA) has been proposed as an environmentally friendly, biocompatible, and economic solution. This study specifically focuses on investigating the parameters for the encapsulation of NPs within a sodium alginate matrix using CaCl2 as cross-linker, including effect of physical shape of encapsulation, effect of sodium alginate and CaCl2 concentration on the encapsulation efficiency and overall adsorption efficiency. Experimental results indicated that the physical form of encapsulation, such as spherical, wire-like, or irregular shape maintained consistent adsorption efficiency, which indicates its versatility. For effective encapsulation of NPs and adsorption, SA and CaCl2 concentration are suggested to be within the range of 0.2-0.3 g and > 0.5 M, respectively..","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256890","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

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