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Understanding Photoinduced Symmetry- Breaking Charge Separation. 理解光诱导对称-破缺电荷分离。
IF 1.1 4区 化学
Chimia Pub Date : 2025-04-30 DOI: 10.2533/chimia.2025.263
Johannes Wega
{"title":"Understanding Photoinduced Symmetry- Breaking Charge Separation.","authors":"Johannes Wega","doi":"10.2533/chimia.2025.263","DOIUrl":"https://doi.org/10.2533/chimia.2025.263","url":null,"abstract":"<p><p>Symmetry-breaking charge separation (SB-CS) is a photoinduced electron transfer reaction in which the chromophore acts as both the acceptor and the donor. This reaction which is still poorly understood may enable long-lived charge separation interesting for many applications. Here we show that SB-CS can be realised bimolecularly with perylene and discuss the factors favouring it. Furthermore, using a pyrene bichromophoric system, we discuss the influence of interchromophore coupling and how the photophysics can be fine-tuned to yield SB-CS over other processes such as excimer formation.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 4","pages":"263-266"},"PeriodicalIF":1.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
When DNA Repair Backfires - Trabectedin Induces DNA Breaks in Active Genes. 当DNA修复事与愿违——Trabectedin诱导活性基因中的DNA断裂。
IF 1.1 4区 化学
Chimia Pub Date : 2025-04-30 DOI: 10.2533/chimia.2025.237
Vakil Takhaveev, Kook Son, Visesato Mor, Hobin Yu, Emma Dillier, Nicola Zilo, Nikolai J L Püllen, Dmitri Ivanov, Helle D Ulrich, Shana J Sturia, Orlando D Schärer
{"title":"When DNA Repair Backfires - Trabectedin Induces DNA Breaks in Active Genes.","authors":"Vakil Takhaveev, Kook Son, Visesato Mor, Hobin Yu, Emma Dillier, Nicola Zilo, Nikolai J L Püllen, Dmitri Ivanov, Helle D Ulrich, Shana J Sturia, Orlando D Schärer","doi":"10.2533/chimia.2025.237","DOIUrl":"https://doi.org/10.2533/chimia.2025.237","url":null,"abstract":"<p><p>Many anticancer drugs are ineffective in tumors that have functional DNA repair mechanisms. In contrast, trabectedin, a tetrahydroisoquinoline alkaloid marine natural product, stands out as it is more lethal to cancer cells with active DNA repair, particularly transcription-coupled nucleotide excision repair (TC-NER), making it an intriguing alternative to standard chemotherapeutic agents. To optimize trabectedin's use in precision oncology, it is essential to understand how its toxicity depends on TC-NER. In this study, we reveal that incomplete TC-NER of trabectedin-DNA adducts generates persistent single-strand breaks (SSBs). These adducts are found to obstruct the second of two sequential NER-mediated DNA incisions. By mapping the 3'-hydroxyl groups of SSBs resulting from the first NER incision at trabectedin-DNA adducts, we achieve genome-wide visualization of TC-NER. Our findings show that trabectedin-induced SSBs predominantly occur in the transcribed strands of active genes, accumulating near transcription start sites. This work provides new insights into how trabectedin can be leveraged for targeted cancer therapies and for studying TC-NER and transcription.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 4","pages":"237-240"},"PeriodicalIF":1.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanopore Technology: When Proteins Analyse Proteins. 纳米孔技术：当蛋白质分析蛋白质。
IF 1.1 4区 化学
Chimia Pub Date : 2025-04-30 DOI: 10.2533/chimia.2025.196
Verena Rukes
{"title":"Nanopore Technology: When Proteins Analyse Proteins.","authors":"Verena Rukes","doi":"10.2533/chimia.2025.196","DOIUrl":"10.2533/chimia.2025.196","url":null,"abstract":"<p><p>Nanopore sensing is an emerging technology that can distinguish subtle differences in molecules and allows the observation of molecular processes. The technique has revolutionized DNA sequencing through long reads of single molecules. Following this success, nanopores are now increasingly applied to protein analysis. Proteins play central roles in cellular function and major diseases, however their analysis using established methods is complicated by the lack of protein-amplification methods. Here, two examples of nanopore-based protein analysis are described: the identification of biomarkers, and the analysis of protein function.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 4","pages":"196-199"},"PeriodicalIF":1.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial. 社论。
IF 1.1 4区 化学
Chimia Pub Date : 2025-04-30 DOI: 10.2533/chimia.2025.193
Ali Coskun, Hans Peter Lüthi
{"title":"Editorial.","authors":"Ali Coskun, Hans Peter Lüthi","doi":"10.2533/chimia.2025.193","DOIUrl":"https://doi.org/10.2533/chimia.2025.193","url":null,"abstract":"","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 4","pages":"193"},"PeriodicalIF":1.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Natural Products as Timeless Remedies - Unlocking Nature's Treasure Trove. 天然产品作为永恒的补救-解锁自然的宝库。
IF 1.1 4区 化学
Chimia Pub Date : 2025-04-30 DOI: 10.2533/chimia.2025.241
Tamara Balsiger, Robin Teufel, Eliane Garo
{"title":"Natural Products as Timeless Remedies - Unlocking Nature's Treasure Trove.","authors":"Tamara Balsiger, Robin Teufel, Eliane Garo","doi":"10.2533/chimia.2025.241","DOIUrl":"https://doi.org/10.2533/chimia.2025.241","url":null,"abstract":"<p><p>Natural products are an essential source of medicines, accounting for a large proportion of approved drugs nowadays. However, the isolation of active natural products from complex extracts is challenging. To address this bottleneck, a drug discovery strategy was developed in our lab, that combines the screening of an in-house crude plant extract library of more than 2,500 samples with an HPLC-based activity profiling approach. This workflow is used routinely in our group and was successfully applied to numerous natural product drug discovery projects.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 4","pages":"241-244"},"PeriodicalIF":1.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing the Brightness of Red-emitting Fluorophores in Aqueous Solution by Molecular Encapsulation. 用分子包封法提高水溶液中红色荧光团的亮度。
IF 1.1 4区 化学
Chimia Pub Date : 2025-04-30 DOI: 10.2533/chimia.2025.259
Liza Briant, Alexandre Fürstenberg
{"title":"Enhancing the Brightness of Red-emitting Fluorophores in Aqueous Solution by Molecular Encapsulation.","authors":"Liza Briant, Alexandre Fürstenberg","doi":"10.2533/chimia.2025.259","DOIUrl":"https://doi.org/10.2533/chimia.2025.259","url":null,"abstract":"<p><p>Fluorescence spectroscopy and microscopy in biomolecular environments are usually performed in aqueous solution and preferably using red-emitting dyes. However, water quenches their fluorescence. We explore in this contribution how host-guest interactions between red-emitting fluorophores and macrocycles such as cyclodextrins and cucurbiturils can prevent quenching by shielding the dyes from water, thereby enhancing their brightness. We successfully apply this strategy in super-resolution imaging.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 4","pages":"259-262"},"PeriodicalIF":1.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Determination of the Absolute Configuration by 3D ED to Elucidate the Atroposelectivity in Aromatic Ring-Opening Metathesis. 用三维能谱法测定绝对构型以阐明芳香开环复合反应中的atropo选择性。
IF 1.1 4区 化学
Chimia Pub Date : 2025-04-30 DOI: 10.2533/chimia.2025.255
Valeriia Hutskalova, Christian Jandl, Alessandro Prescimone, Christof Sparr
{"title":"Determination of the Absolute Configuration by 3D ED to Elucidate the Atroposelectivity in Aromatic Ring-Opening Metathesis.","authors":"Valeriia Hutskalova, Christian Jandl, Alessandro Prescimone, Christof Sparr","doi":"10.2533/chimia.2025.255","DOIUrl":"https://doi.org/10.2533/chimia.2025.255","url":null,"abstract":"<p><p>The determination of the absolute configuration of molecules bearing different stereogenic elements represents a fundamental and indispensable task in the field of stereochemistry. Whereas X-ray crystallographic analysis has been established as a broadly utilized and reliable technique to achieve this goal, limitations remain arising from the demanding requirements for the size and diffraction quality of the analyzed crystals. As an emerging technique, 3D microcrystal electron diffraction (3D ED) has increasingly been recognized to complement single crystal X-ray diffraction (SC-XRD). Having encountered challenges in determining the absolute configuration for the products obtained during the development of atroposelective aromatic ring-opening metathesis (AArROM), we herein describe in detail, how 3D ED allowed an assignment, which proved unfeasible using the conventional approach with X-ray crystallography.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 4","pages":"255-258"},"PeriodicalIF":1.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reversible Covalent Reactions of Aldehydes and Salicylaldehydes Using a Lysine-Model Substrate. 用赖氨酸模型底物进行醛和水杨醛的可逆共价反应。
IF 1.1 4区 化学
Chimia Pub Date : 2025-03-26 DOI: 10.2533/chimia.2025.152
Cécile Delmas, Emine Sager, Chrystele Henry, Ulrich Hassiepen, Philip R Skaanderup, Isabel Kerschgens
{"title":"Reversible Covalent Reactions of Aldehydes and Salicylaldehydes Using a Lysine-Model Substrate.","authors":"Cécile Delmas, Emine Sager, Chrystele Henry, Ulrich Hassiepen, Philip R Skaanderup, Isabel Kerschgens","doi":"10.2533/chimia.2025.152","DOIUrl":"10.2533/chimia.2025.152","url":null,"abstract":"<p><p>Covalent modification of lysine residues has gained significant attention due to its potential application in drug development and chemical biology. Lysine is an essential amino acid, abundant in proteins, and plays a critical role in many biological processes. In this study, we investigated aldehydes for imine-based chemistries and their reactivity profiles using a lysine-surrogate. By monitoring reactions of various aldehydes and salicylaldehydes over time, we determined dissociation constants (KD) for each warhead, reflecting the binding affinity towards the surrogate substrate. Strikingly, our data revealed remarkable differences in affinity depending on the substitution of the warheads. Additionally, we analyzed the kinetic profile of selected aldehydes and salicylaldehydes, which revealed significant disparity in their reaction kinetics. Aldehydes reacted quickly, reaching equilibrium rapidly, whereas salicylaldehydes exhibited considerably slower reaction times, in some cases requiring several hours to reach equilibrium. These differences emphasize how the nature of the warhead structure influences the kinetics of covalent binding to lysine residues. Overall, our study provides valuable insights into the application of reversible covalency to target lysines with reactive warheads that can further inspire development of innovative chemical modifications for drug discovery and chemical biology.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 3","pages":"152-157"},"PeriodicalIF":1.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oligonucleotide-based PROTACs to Degrade RNA- and DNA-Binding Proteins. 基于寡核苷酸的PROTACs降解RNA和dna结合蛋白。
IF 1.1 4区 化学
Chimia Pub Date : 2025-03-26 DOI: 10.2533/chimia.2025.167
Céline N Weller, Jonathan Hall
{"title":"Oligonucleotide-based PROTACs to Degrade RNA- and DNA-Binding Proteins.","authors":"Céline N Weller, Jonathan Hall","doi":"10.2533/chimia.2025.167","DOIUrl":"10.2533/chimia.2025.167","url":null,"abstract":"<p><p>Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules that sequester the endogenous protein degradation machinery of cells to induce degradation of targeted proteins. By bringing a target protein and a ubiquitin E3 ligase into close proximity, ubiquitin monomers can be transferred onto surface lysines of the protein, which is subsequently degraded by the proteasome. The functions of RNA- and DNA-binding proteins have been especially hard to modulate with small molecules. However, oligonucleotides that bind RNA- or DNA-binding proteins can be turned into oligonucleotide-based PROTACs to direct ubiquitination and degradation of these proteins. Here we summarize the current state of the field of oligonucleotide-based PROTACs that target RNA- or DNA-binding proteins.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 3","pages":"167-171"},"PeriodicalIF":1.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Towards the Rational Design of Monovalent Degraders: Lessons Learnt from Cyclin K Degraders. 单价降解剂的合理设计：Cyclin K降解剂的经验教训。
IF 1.1 4区 化学
Chimia Pub Date : 2025-03-26 DOI: 10.2533/chimia.2025.162
Katie L Thomas, Benjamin R Bellenie, Olivia W Rossanese
{"title":"Towards the Rational Design of Monovalent Degraders: Lessons Learnt from Cyclin K Degraders.","authors":"Katie L Thomas, Benjamin R Bellenie, Olivia W Rossanese","doi":"10.2533/chimia.2025.162","DOIUrl":"10.2533/chimia.2025.162","url":null,"abstract":"<p><p>Monovalent degraders can enhance pre-existing surface complementarity between a target protein and a ligase to induce target degradation via the proteasome. For the most part, degraders have been discovered serendipitously and structure-activity relationship (SAR) studies have been limited, making it difficult to rationally design new compounds. Here we discuss how work on the SAR of cyclin K degraders demonstrates that a broad range of compounds can stabilise protein-protein interactions to induce degradation and how it lays the foundation for further monovalent degrader discovery.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 3","pages":"162-166"},"PeriodicalIF":1.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","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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