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Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-17 DOI: 10.1021/acs.chemrev.4c00595
Lisha Ou, Mekedlawit T. Setegne, Jeandele Elliot, Fangfang Shen, Laura M. K. Dassama
The nascent field of targeted protein degradation (TPD) could revolutionize biomedicine due to the ability of degrader molecules to selectively modulate disease-relevant proteins. A key limitation to the broad application of TPD is its dependence on small-molecule ligands to target proteins of interest. This leaves unstructured proteins or those lacking defined cavities for small-molecule binding out of the scope of many TPD technologies. The use of proteins, peptides, and nucleic acids (otherwise known as “biologics”) as the protein-targeting moieties in degraders addresses this limitation. In the following sections, we provide a comprehensive and critical review of studies that have used proteins and peptides to mediate the degradation and hence the functional control of otherwise challenging disease-relevant protein targets. We describe existing platforms for protein/peptide-based ligand identification and the drug delivery systems that might be exploited for the delivery of biologic-based degraders. Throughout the Review, we underscore the successes, challenges, and opportunities of using protein-based degraders as chemical biology tools to spur discoveries, elucidate mechanisms, and act as a new therapeutic modality.
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引用次数: 0
Hydrolysis, Ligand Exchange, and Redox Properties of Vanadium Compounds: Implications of Solution Transformation on Biological, Therapeutic, and Environmental Applications
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-16 DOI: 10.1021/acs.chemrev.4c00475
Rupam Dinda, Eugenio Garribba, Daniele Sanna, Debbie C. Crans, João Costa Pessoa
Vanadium is a transition metal with important industrial, technological, biological, and biomedical applications widespread in the environment and in living beings. The different reactions that vanadium compounds (VCs) undergo in the presence of proteins, nucleic acids, lipids and metabolites under mild physiological conditions are reviewed. In the environment vanadium is present naturally or through anthropogenic sources, the latter having an environmental impact caused by the dispersion of VCs in the atmosphere and aquifers. Vanadium has a versatile chemistry with interconvertible oxidation states, variable coordination number and geometry, and ability to form polyoxidovanadates with various nuclearity and structures. If a VC is added to a water-containing environment it can undergo hydrolysis, ligand-exchange, redox, and other types of changes, determined by the conditions and speciation chemistry of vanadium. Importantly, the solution is likely to differ from the VC introduced into the system and varies with concentration. Here, vanadium redox, hydrolytic and ligand-exchange chemical reactions, the influence of pH, concentration, salt, specific solutes, biomolecules, and VCs on the speciation are described. One of our goals with this work is highlight the need for assessment of the VC speciation, so that beneficial or toxic species might be identified and mechanisms of action be elucidated.
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引用次数: 0
The Impact of Electric Fields on Processes at Electrode Interfaces
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-16 DOI: 10.1021/acs.chemrev.4c00487
Zhuoran Long, Jinhui Meng, Lydia R. Weddle, Pablo E. Videla, Jan Paul Menzel, Delmar G. A. Cabral, Jinchan Liu, Tianyin Qiu, Joseph M. Palasz, Dhritiman Bhattacharyya, Clifford P. Kubiak, Victor S. Batista, Tianquan Lian
The application of external electric fields to influence chemical reactions at electrode interfaces has attracted considerable interest in recent years. However, the design of electric fields to achieve highly efficient and selective catalytic systems, akin to the optimized fields found at enzyme active sites, remains a significant challenge. Consequently, there has been substantial effort in probing and understanding the interfacial electric fields at electrode/electrolyte interfaces and their effect on adsorbates. In this review, we examine recent advances in experimental, computational, and theoretical studies of the interfacial electric field, the origin of the vibrational Stark effect of adsorbates on electrode surfaces, and the effects of electric fields on reactions at electrode/electrolyte interfaces. We also discuss recent advances in control of charge transfer and chemical reactions using magnetic fields. Finally, we outline perspectives on key areas for future studies.
近年来,应用外部电场来影响电极界面上的化学反应引起了人们的极大兴趣。然而,如何设计电场以实现高效和选择性催化系统(类似于酶活性位点的优化电场),仍然是一项重大挑战。因此,人们在探测和了解电极/电解质界面电场及其对吸附剂的影响方面付出了巨大努力。在本综述中,我们将探讨界面电场的实验、计算和理论研究的最新进展,电极表面吸附剂振动斯塔克效应的起源,以及电场对电极/电解质界面反应的影响。我们还讨论了利用磁场控制电荷转移和化学反应的最新进展。最后,我们对未来研究的关键领域进行了展望。
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引用次数: 0
Interfacial Catalysis at Atomic Level
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-16 DOI: 10.1021/acs.chemrev.4c00618
Mi Peng, Chengyu Li, Zhaohua Wang, Maolin Wang, Qingxin Zhang, Bingjun Xu, Mufan Li, Ding Ma
Heterogeneous catalysts are pivotal to the chemical and energy industries, which are central to a multitude of industrial processes. Large-scale industrial catalytic processes rely on special structures at the nano- or atomic level, where reactions proceed on the so-called active sites of heterogeneous catalysts. The complexity of these catalysts and active sites often lies in the interfacial regions where different components in the catalysts come into contact. Recent advances in synthetic methods, characterization technologies, and reaction kinetics studies have provided atomic-scale insights into these critical interfaces. Achieving atomic precision in interfacial engineering allows for the manipulation of electronic profiles, adsorption patterns, and surface motifs, deepening our understanding of reaction mechanisms at the atomic or molecular level. This mechanistic understanding is indispensable not only for fundamental scientific inquiry but also for the design of the next generation of highly efficient industrial catalysts. This review examines the latest developments in atomic-scale interfacial engineering, covering fundamental concepts, catalyst design, mechanistic insights, and characterization techniques, and shares our perspective on the future trajectory of this dynamic research field.
异相催化剂在化学和能源工业中举足轻重,是众多工业流程的核心。大规模工业催化过程依赖于纳米级或原子级的特殊结构,反应在异相催化剂的所谓活性位点上进行。这些催化剂和活性位点的复杂性往往在于催化剂中不同成分接触的界面区域。合成方法、表征技术和反应动力学研究方面的最新进展为这些关键界面提供了原子尺度的洞察力。在界面工程中实现原子精度,可以对电子剖面、吸附模式和表面图案进行操作,从而加深我们对原子或分子水平反应机制的理解。这种对机理的理解不仅对基础科学研究不可或缺,而且对设计下一代高效工业催化剂也不可或缺。这篇综述探讨了原子尺度界面工程学的最新发展,涵盖基本概念、催化剂设计、机理认识和表征技术,并分享了我们对这一充满活力的研究领域未来发展轨迹的看法。
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引用次数: 0
Covalent Template-Directed Synthesis: A Powerful Tool for the Construction of Complex Molecules 共价模板指导合成:构建复杂分子的强大工具
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-13 DOI: 10.1021/acs.chemrev.4c00505
Peter Bolgar, Mohit Dhiman, Diego Núñez-Villanueva, Christopher A. Hunter
Template-directed synthesis has become a powerful methodology to access complex molecules. Noncovalent templating has been widely used in the last few decades, but less attention has been paid to covalent template-directed synthesis, despite the fact that this methodology was used for the first reported synthesis of a catenane. This review highlights the evolution of covalent templating over the last 60 years, thereby providing a toolbox for the design of efficient covalent templating processes. Covalent templating represents a useful synthetic tool for accessing complex molecules, and the examples described here include the synthesis of macrocycles, mechanically interlocked molecules, linear oligomers, polydisperse linear polymers, and cross-linked polymer networks.
{"title":"Covalent Template-Directed Synthesis: A Powerful Tool for the Construction of Complex Molecules","authors":"Peter Bolgar, Mohit Dhiman, Diego Núñez-Villanueva, Christopher A. Hunter","doi":"10.1021/acs.chemrev.4c00505","DOIUrl":"https://doi.org/10.1021/acs.chemrev.4c00505","url":null,"abstract":"Template-directed synthesis has become a powerful methodology to access complex molecules. Noncovalent templating has been widely used in the last few decades, but less attention has been paid to covalent template-directed synthesis, despite the fact that this methodology was used for the first reported synthesis of a catenane. This review highlights the evolution of covalent templating over the last 60 years, thereby providing a toolbox for the design of efficient covalent templating processes. Covalent templating represents a useful synthetic tool for accessing complex molecules, and the examples described here include the synthesis of macrocycles, mechanically interlocked molecules, linear oligomers, polydisperse linear polymers, and cross-linked polymer networks.","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"43 1","pages":""},"PeriodicalIF":62.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Synthetic Lipid Biology
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-13 DOI: 10.1021/acs.chemrev.4c00761
Po-Hsun Brian Chen, Xiang-Ling Li, Jeremy M. Baskin
Cells contain thousands of different lipids. Their rapid and redundant metabolism, dynamic movement, and many interactions with other biomolecules have justly earned lipids a reputation as a vexing class of molecules to understand. Further, as the cell’s hydrophobic metabolites, lipids assemble into supramolecular structures─most commonly bilayers, or membranes─from which they carry out myriad biological functions. Motivated by this daunting complexity, researchers across disciplines are bringing order to the seeming chaos of biological lipids and membranes. Here, we formalize these efforts as “synthetic lipid biology”. Inspired by the idea, central to synthetic biology, that our abilities to understand and build biological systems are intimately connected, we organize studies and approaches across numerous fields to create, manipulate, and analyze lipids and biomembranes. These include construction of lipids and membranes from scratch using chemical and chemoenzymatic synthesis, editing of pre-existing membranes using optogenetics and protein engineering, detection of lipid metabolism and transport using bioorthogonal chemistry, and probing of lipid–protein interactions and membrane biophysical properties. What emerges is a portrait of an incipient field where chemists, biologists, physicists, and engineers work together in proximity─like lipids themselves─to build a clearer description of the properties, behaviors, and functions of lipids and membranes.
{"title":"Synthetic Lipid Biology","authors":"Po-Hsun Brian Chen, Xiang-Ling Li, Jeremy M. Baskin","doi":"10.1021/acs.chemrev.4c00761","DOIUrl":"https://doi.org/10.1021/acs.chemrev.4c00761","url":null,"abstract":"Cells contain thousands of different lipids. Their rapid and redundant metabolism, dynamic movement, and many interactions with other biomolecules have justly earned lipids a reputation as a vexing class of molecules to understand. Further, as the cell’s hydrophobic metabolites, lipids assemble into supramolecular structures─most commonly bilayers, or membranes─from which they carry out myriad biological functions. Motivated by this daunting complexity, researchers across disciplines are bringing order to the seeming chaos of biological lipids and membranes. Here, we formalize these efforts as “synthetic lipid biology”. Inspired by the idea, central to synthetic biology, that our abilities to understand and build biological systems are intimately connected, we organize studies and approaches across numerous fields to create, manipulate, and analyze lipids and biomembranes. These include construction of lipids and membranes from scratch using chemical and chemoenzymatic synthesis, editing of pre-existing membranes using optogenetics and protein engineering, detection of lipid metabolism and transport using bioorthogonal chemistry, and probing of lipid–protein interactions and membrane biophysical properties. What emerges is a portrait of an incipient field where chemists, biologists, physicists, and engineers work together in proximity─like lipids themselves─to build a clearer description of the properties, behaviors, and functions of lipids and membranes.","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"22 1","pages":""},"PeriodicalIF":62.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
The Carbene Chemistry of N-Sulfonyl Hydrazones: The Past, Present, and Future
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-10 DOI: 10.1021/acs.chemrev.4c00742
Xiaolong Zhang, Paramasivam Sivaguru, Yongzhen Pan, Nan Wang, Wenjie Zhang, Xihe Bi
N-Sulfonyl hydrazones have been extensively used as operationally safe carbene precursors in modern organic synthesis due to their ready availability, facile functionalization, and environmental benignity. Over the past two decades, there has been tremendous progress in the carbene chemistry of N-sulfonyl hydrazones in the presence of transition metal catalysts, under metal-free conditions, or using photocatalysts under photoirradiation conditions. Many carbene transfer reactions of N-sulfonyl hydrazones are unique and cannot be achieved by any alternative methods. The discovery of novel N-sulfonyl hydrazones and the development of highly enantioselective new reactions and skeletal editing reactions represent the notable recent achievements in the carbene chemistry of N-sulfonyl hydrazones. This review describes the overall progress made in the carbene chemistry of N-sulfonyl hydrazones, organized based on reaction types, spotlighting the current state-of-the-art and remaining challenges to be addressed in the future. Special emphasis is devoted to identifying, describing, and comparing the scope and limitations of current methodologies, key mechanistic scenarios, and potential applications in the synthesis of complex molecules.
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引用次数: 0
Targeted Covalent Modification Strategies for Drugging the Undruggable Targets
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-07 DOI: 10.1021/acs.chemrev.4c00745
Tomonori Tamura, Masaharu Kawano, Itaru Hamachi
The term “undruggable” refers to proteins or other biological targets that have been historically challenging to target with conventional drugs or therapeutic strategies because of their structural, functional, or dynamic properties. Drugging such undruggable targets is essential to develop new therapies for diseases where current treatment options are limited or nonexistent. Thus, investigating methods to achieve such drugging is an important challenge in medicinal chemistry. Among the numerous methodologies for drug discovery, covalent modification of therapeutic targets has emerged as a transformative strategy. The covalent attachment of diverse functional molecules to targets provides a powerful platform for creating highly potent drugs and chemical tools as well the ability to provide valuable information on the structures and dynamics of undruggable targets. In this review, we summarize recent examples of chemical methods for the covalent modification of proteins and other biomolecules for the development of new therapeutics and to overcome drug discovery challenges and highlight how such methods contribute toward the drugging of undruggable targets. In particular, we focus on the use of covalent chemistry methods for the development of covalent drugs, target identification, drug screening, artificial modulation of post-translational modifications, cancer specific chemotherapies, and nucleic acid-based therapeutics.
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引用次数: 0
Phase Control in Monometallic and Alloy Nanomaterials
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-03 DOI: 10.1021/acs.chemrev.4c00368
Kohei Kusada, Hiroshi Kitagawa
Metal nanomaterials with unconventional phases have been recently developed with a variety of methods and exhibit novel and attractive properties such as high activities for various catalytic reactions and magnetic properties. In this review, we discuss the progress and the trends in strategies for synthesis, crystal structure, and properties of phase-controlled metal nanomaterials in terms of elements and the combination of alloys. We begin with a brief introduction of the anomalous phase behavior derived from the nanosize effect and general crystal structures observed in metal nanomaterials. Then, phase control in monometallic nanomaterials with respect to each element and alloy nanomaterials classified into three types based on their crystal structures is discussed. In the end, all the content introduced in this review is summarized, and challenges for advanced phase control are discussed.
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引用次数: 0
Metal Ion Signaling in Biomedicine
IF 62.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-01-02 DOI: 10.1021/acs.chemrev.4c00577
Raphaël Rodriguez, Sebastian Müller, Ludovic Colombeau, Stéphanie Solier, Fabien Sindikubwabo, Tatiana Cañeque
Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species are defined by their genomes, and differences between individuals within a given species directly result from variations in their genetic codes. While genetic alterations can give rise to disease-causing acquisitions of distinct cell identities, it is now well-established that biochemical imbalances within a cell can also lead to cellular dysfunction and diseases. Specifically, nongenetic chemical events orchestrate cell metabolism and transcriptional programs that govern functional cell identity. Thus, imbalances in cell signaling, which broadly defines the conversion of extracellular signals into intracellular biochemical changes, can also contribute to the acquisition of diseased cell states. Metal ions exhibit unique chemical properties that can be exploited by the cell. For instance, metal ions maintain the ionic balance within the cell, coordinate amino acid residues or nucleobases altering folding and function of biomolecules, or directly catalyze specific chemical reactions. Thus, metals are essential cell signaling effectors in normal physiology and disease. Deciphering metal ion signaling is a challenging endeavor that can illuminate pathways to be targeted for therapeutic intervention. Here, we review key cellular processes where metal ions play essential roles and describe how targeting metal ion signaling pathways has been instrumental to dissecting the biochemistry of the cell and how this has led to the development of effective therapeutic strategies.
{"title":"Metal Ion Signaling in Biomedicine","authors":"Raphaël Rodriguez, Sebastian Müller, Ludovic Colombeau, Stéphanie Solier, Fabien Sindikubwabo, Tatiana Cañeque","doi":"10.1021/acs.chemrev.4c00577","DOIUrl":"https://doi.org/10.1021/acs.chemrev.4c00577","url":null,"abstract":"Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species are defined by their genomes, and differences between individuals within a given species directly result from variations in their genetic codes. While genetic alterations can give rise to disease-causing acquisitions of distinct cell identities, it is now well-established that biochemical imbalances within a cell can also lead to cellular dysfunction and diseases. Specifically, nongenetic chemical events orchestrate cell metabolism and transcriptional programs that govern functional cell identity. Thus, imbalances in cell signaling, which broadly defines the conversion of extracellular signals into intracellular biochemical changes, can also contribute to the acquisition of diseased cell states. Metal ions exhibit unique chemical properties that can be exploited by the cell. For instance, metal ions maintain the ionic balance within the cell, coordinate amino acid residues or nucleobases altering folding and function of biomolecules, or directly catalyze specific chemical reactions. Thus, metals are essential cell signaling effectors in normal physiology and disease. Deciphering metal ion signaling is a challenging endeavor that can illuminate pathways to be targeted for therapeutic intervention. Here, we review key cellular processes where metal ions play essential roles and describe how targeting metal ion signaling pathways has been instrumental to dissecting the biochemistry of the cell and how this has led to the development of effective therapeutic strategies.","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"27 1","pages":""},"PeriodicalIF":62.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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Chemical Reviews
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