发布求助
文献互助 智能选刊 最新文献

Chimia最新文献

筛选
英文 中文
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":"https://doi.org/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
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":"https://doi.org/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
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":"https://doi.org/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
Precision Probing of O-GalNAc Glycosylation Using Bump-and-Hole Engineering. 利用凹凸孔工程精确探测O-GalNAc糖基化。
IF 1.1 4区 化学
Chimia Pub Date : 2025-03-26 DOI: 10.2533/chimia.2025.146
Abdul Zafar, Benjamin Schumann
{"title":"Precision Probing of O-GalNAc Glycosylation Using Bump-and-Hole Engineering.","authors":"Abdul Zafar, Benjamin Schumann","doi":"10.2533/chimia.2025.146","DOIUrl":"https://doi.org/10.2533/chimia.2025.146","url":null,"abstract":"<p><p>Glycosylation is a profound influencer of glycoprotein function. Glycans have a critical impact on health and disease, yet the tools to study them have trailed behind proteins and nucleic acids. O-GalNAc glycosylation involves the addition of N-acetylgalactosamine (GalNAc) to protein substrates. Dysregulation of O-GalNAc glycosylation is implicated in many pathologies such as cancer. Studying O-GalNAc glycosylation is complicated by the lack of a consensus sequence for initiation and the complex interdependence between a large family of 20 GalNAc transferases (GalNAc-Ts) in human cells. These issues necessitate precise methods of interrogating enzyme function. Herein, we discuss our own advances into the generation of precision tools to study O-GalNAc glycosylation and other glycosylation types. We discuss the use of bump-and-hole engineering to illuminate the roles of individual GalNAc-Ts. Engineering biosynthetic pathways enables cell line-specific uptake of chemical, editable sugars in co-culture settings. We provide an insight into the state-of-the-art in this field.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 3","pages":"146-151"},"PeriodicalIF":1.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742466","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 : 2025-03-26 DOI: 10.2533/chimia.2025.125
Amandine Kolleth, Vlad Pascanu
{"title":"Editorial.","authors":"Amandine Kolleth, Vlad Pascanu","doi":"10.2533/chimia.2025.125","DOIUrl":"https://doi.org/10.2533/chimia.2025.125","url":null,"abstract":"","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 3","pages":"125"},"PeriodicalIF":1.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742459","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
Recent Advances in CBP/EP300 Degraders. CBP/EP300降解剂的研究进展
IF 1.1 4区 化学
Chimia Pub Date : 2025-03-26 DOI: 10.2533/chimia.2025.137
Leonardo Palaferri, Iván Cheng-Sánchez, Cristina Nevado
{"title":"Recent Advances in CBP/EP300 Degraders.","authors":"Leonardo Palaferri, Iván Cheng-Sánchez, Cristina Nevado","doi":"10.2533/chimia.2025.137","DOIUrl":"https://doi.org/10.2533/chimia.2025.137","url":null,"abstract":"<p><p>Targeted protein degradation (TPD) has emerged as an innovative therapeutic strategy, offering advantage over traditional approaches rooted in small-molecule inhibitors. Among the various modalities in TPD, proteolysis targeting chimeras (PROTACs) and molecular glue degraders (MGDs) have arisen as leading modalities, distinguished by their ability to induce protein degradation via the ubiquitin-proteasome system (UPS). In recent years, extensive research has focused on developing degraders targeting CREB-binding protein (CBP) and E1A-associated protein (EP300) - two homologous multidomain enzymes critical for enhancer-mediated transcription. This review explores the state of the art in CBP/EP300 degraders, underscoring the significant potential of these synthetic bifunctional compounds as innovative chemical tools and highly promising anticancer agents.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 3","pages":"137-145"},"PeriodicalIF":1.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742474","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
Challenges and Opportunities in DNA Encoded Library Screens. DNA编码库屏幕的挑战与机遇。
IF 1.1 4区 化学
Chimia Pub Date : 2025-03-26 DOI: 10.2533/chimia.2025.158
Basilius Sauter, Pinwen Cai, Koder Dagher, Chiara Disraeli, Athira Kakkolliyil Prakash, Lukas Schneider, Ángel Cores Esperon, Dennis Gillingham
{"title":"Challenges and Opportunities in DNA Encoded Library Screens.","authors":"Basilius Sauter, Pinwen Cai, Koder Dagher, Chiara Disraeli, Athira Kakkolliyil Prakash, Lukas Schneider, Ángel Cores Esperon, Dennis Gillingham","doi":"10.2533/chimia.2025.158","DOIUrl":"https://doi.org/10.2533/chimia.2025.158","url":null,"abstract":"<p><p>In our lab we have been developing techniques that attempt to capture or amplify signals in pooled compound mixtures for several years. DNA encoded libraries (DELs) are the most widely used pooled mixtures in early drug discovery. DELs are massive collections of small molecules, where each individual molecule is covalently linked to a unique DNA strand that can serve as an identification tag by sequencing. The industry standard for selecting DELs is affinity enrichment, which inherently can only search for direct binding. We outline here two of the ways that we are attempting to extend the potential of DEL screens into new areas.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 3","pages":"158-161"},"PeriodicalIF":1.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742454","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
Control of Therapeutic Activity through Programmed Assembly. 通过程序化组装控制治疗活动。
IF 1.1 4区 化学
Chimia Pub Date : 2025-03-26 DOI: 10.2533/chimia.2025.128
Millicent Dockerill, Nicolas Winssinger
{"title":"Control of Therapeutic Activity through Programmed Assembly.","authors":"Millicent Dockerill, Nicolas Winssinger","doi":"10.2533/chimia.2025.128","DOIUrl":"https://doi.org/10.2533/chimia.2025.128","url":null,"abstract":"<p><p>This review explores the control of therapeutic activity through programmed assembly of supramolecular systems. We examine the use of nucleic acids as scaffolds to create tailored assemblies of ligands, including glycan and peptide-based systems, drug-like small molecules or reagents for proximity-induced reactions. We discuss the principles of cooperativity in multivalent interactions, emphasizing their potential to enhance binding affinity and therapeutic efficacy and the opportunity to control their activity through strand displacement. We highlight seminal studies and illustrative case examples and address the challenges faced in translating these designs into clinical applications. Furthermore, we explore recent advancements that demonstrate successful in vivo applications, particularly in the context of anticoagulation therapies. This review aims to provide insights into the future of responsive therapeutic systems that leverage the programmability of supramolecular assemblies to develop potent and adaptable therapeutics.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 3","pages":"128-136"},"PeriodicalIF":1.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742456","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
On Paper Diagnostics: A Brief History and Future Perspectives. 论文诊断学：简史与未来展望。
IF 1.1 4区 化学
Chimia Pub Date : 2025-02-26 DOI: 10.2533/chimia.2025.29
Nathan Khosla, Andrew DeMello, Daniel Richards
{"title":"On Paper Diagnostics: A Brief History and Future Perspectives.","authors":"Nathan Khosla, Andrew DeMello, Daniel Richards","doi":"10.2533/chimia.2025.29","DOIUrl":"https://doi.org/10.2533/chimia.2025.29","url":null,"abstract":"<p><p>For centuries, diagnostic technologies have played a key role in medicine. Effective diagnostics can help clinicians identify the presence and extent of disease in their patients, as well as their general health. Precipitated by advances in biochemistry, chemistry, and engineering, the 20th and 21st centuries have witnessed rapid advancement in diagnostic technologies. However, these improvements have brought increased complexity and a corresponding move towards more centralized and specialized laboratories. This has led to significant healthcare disparities between high- and low/middle-income regions. However, with the introduction of paper-based diagnostics this paradigm has begun to shift, with new assay formats designed for point-of-care (PoC) or at-home use. By leveraging innovations from multiple fields, these paper-based tests can translate complex assay procedures into easy-to-use, single-step tests for the end user. In this review, we summarize the interdisciplinary beginnings of paper-based diagnostics, detailing their development through market introduction and commercial successes, and discuss the current state-of-the-art. Finally, we highlight areas for improvement and propose pathways that could enable increasingly complex chemistries to be performed on simple paper-based devices.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 1-2","pages":"29-35"},"PeriodicalIF":1.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536370","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
Portable and Handheld Raman Instruments Open a Multitude of Applications. 便携式和手持拉曼仪器打开了大量的应用。
IF 1.1 4区 化学
Chimia Pub Date : 2025-02-26 DOI: 10.2533/chimia.2025.46
Christoph Jansen
{"title":"Portable and Handheld Raman Instruments Open a Multitude of Applications.","authors":"Christoph Jansen","doi":"10.2533/chimia.2025.46","DOIUrl":"https://doi.org/10.2533/chimia.2025.46","url":null,"abstract":"<p><p>Fundamental science can sometimes take a long time until it is useful for practical applications, as was the case for Raman spectroscopy. For a long time, it lacked powerful excitation sources and sensitive detectors. However as technology evolved, the number of exciting applications has boomed. Modern Raman spectroscopy has significant advantages, especially in sample preparation. Handheld Raman devices can be very compact and therefore be easily taken to the sample instead of bringing the sample to the lab. Non-destructive measurements obviously are important in gemmology and mineralogy, even in space. In the field of archaeology, pigments in precious ancient paintings, scrolls or books can be identified. This application is also used to identify fraud and falsification and in studies from a medical school they have reported that Raman spectroscopy can be applied to distinguish cancerous tissue from healthy tissue. Due to the mobility and ruggedness of the handheld hardware, Raman spectroscopy can be used for police, firefighters, and military applications for identification of explosives and illicit drugs or warfare substances. With SERS (Surface Enhanced Raman Spectroscopy), Raman spectroscopy can even be used for trace analysis. The SERS effect enhances the sensitivity of the Raman signal by a factor of up to 107. This enables, for example, measuring pesticide residuals on fruit or vegetable surfaces for food safety. It can also be used to identify traces of drugs, e.g. in urine. However, one of the most common Raman-applications is the identity check or verification of incoming goods (RMID) in the pharma industries, directly in the warehouse. Users appreciate the ease of use and the ruggedness of the Raman hardware.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 1-2","pages":"46-51"},"PeriodicalIF":1.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536373","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
下一页 尾页
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整，为了账户安全，请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们：info@booksci.cn Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号：481959085
Book学术官方微信