Chemical Reviews最新文献

{"title":"Drugging Challenging Cancer Targets Using Fragment-Based Methods","authors":"Stephen W. Fesik","doi":"10.1021/acs.chemrev.4c00892","DOIUrl":"https://doi.org/10.1021/acs.chemrev.4c00892","url":null,"abstract":"There are many highly validated cancer targets that are difficult or impossible to drug due to the absence of suitable pockets that can bind small molecules. Fragment-based methods have been shown to be a useful approach for identifying ligands to proteins that were previously thought to be undruggable. In this review, I will give an overview of fragment-based ligand discovery and provide examples from our own work on how fragment-based methods were used to discover high affinity ligands for challenging cancer drug targets.","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"67 1","pages":""},"PeriodicalIF":62.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561167","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}

{"title":"Drugging Challenging Cancer Targets Using Fragment-Based Methods","authors":"Stephen W. Fesik*,&nbsp;","doi":"10.1021/acs.chemrev.4c0089210.1021/acs.chemrev.4c00892","DOIUrl":"https://doi.org/10.1021/acs.chemrev.4c00892https://doi.org/10.1021/acs.chemrev.4c00892","url":null,"abstract":"<p >There are many highly validated cancer targets that are difficult or impossible to drug due to the absence of suitable pockets that can bind small molecules. Fragment-based methods have been shown to be a useful approach for identifying ligands to proteins that were previously thought to be undruggable. In this review, I will give an overview of fragment-based ligand discovery and provide examples from our own work on how fragment-based methods were used to discover high affinity ligands for challenging cancer drug targets.</p>","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"125 6","pages":"3586–3594 3586–3594"},"PeriodicalIF":51.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrev.4c00892","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connecting the Dots: Sintering of Liquid Metal Particles for Soft and Stretchable Conductors","authors":"Simok Lee, Syed Ahmed Jaseem, Nurit Atar, Meixiang Wang, Jeong Yong Kim, Mohammadreza Zare, Sooyoung Kim, Michael D. Bartlett, Jae-Woong Jeong, Michael D. Dickey","doi":"10.1021/acs.chemrev.4c00850","DOIUrl":"https://doi.org/10.1021/acs.chemrev.4c00850","url":null,"abstract":"This review focuses on the sintering of liquid metal particles (LMPs). Here, sintering means the partial merging or connecting of particles (or droplets) to form a network of percolated and, thus, conductive electrical pathways. LMPs are attractive materials because they can be suspended in a carrier fluid to create printable inks or distributed in an elastomer to create soft, stretchable composites. However, films and traces of LMPs are not typically conductive as fabricated due to the native oxide that forms on the surface of the particles. In the case of composites, polymers can also get between particles, making sintering more challenging. Sintering can be done via a variety of ways, such as mechanical, thermal, and chemical processing. This review discusses the mechanisms to sinter these particles, patterning techniques that use sintering, unique properties of sintered LMPs, and their practical applications in fields such as stretchable electronics, soft robotics, and active materials.","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"32 1","pages":""},"PeriodicalIF":62.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539258","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}

{"title":"Connecting the Dots: Sintering of Liquid Metal Particles for Soft and Stretchable Conductors","authors":"Simok Lee,&nbsp;Syed Ahmed Jaseem,&nbsp;Nurit Atar,&nbsp;Meixiang Wang,&nbsp;Jeong Yong Kim,&nbsp;Mohammadreza Zare,&nbsp;Sooyoung Kim,&nbsp;Michael D. Bartlett,&nbsp;Jae-Woong Jeong and Michael D. Dickey*,&nbsp;","doi":"10.1021/acs.chemrev.4c0085010.1021/acs.chemrev.4c00850","DOIUrl":"https://doi.org/10.1021/acs.chemrev.4c00850https://doi.org/10.1021/acs.chemrev.4c00850","url":null,"abstract":"<p >This review focuses on the sintering of liquid metal particles (LMPs). Here, sintering means the partial merging or connecting of particles (or droplets) to form a network of percolated and, thus, conductive electrical pathways. LMPs are attractive materials because they can be suspended in a carrier fluid to create printable inks or distributed in an elastomer to create soft, stretchable composites. However, films and traces of LMPs are not typically conductive as fabricated due to the native oxide that forms on the surface of the particles. In the case of composites, polymers can also get between particles, making sintering more challenging. Sintering can be done via a variety of ways, such as mechanical, thermal, and chemical processing. This review discusses the mechanisms to sinter these particles, patterning techniques that use sintering, unique properties of sintered LMPs, and their practical applications in fields such as stretchable electronics, soft robotics, and active materials.</p>","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"125 6","pages":"3551–3585 3551–3585"},"PeriodicalIF":51.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696566","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}

{"title":"Design Approaches That Utilize Ionic Interactions to Control Selectivity in Transition Metal Catalysis","authors":"Hannah K. Adams, Max Kadarauch, Nicholas J. Hodson, Arthur R. Lit, Robert J. Phipps","doi":"10.1021/acs.chemrev.4c00849","DOIUrl":"https://doi.org/10.1021/acs.chemrev.4c00849","url":null,"abstract":"The attractive force between two oppositely charged ions can constitute a powerful design tool in selective catalysis. Enzymes make extensive use of ionic interactions alongside a variety of other noncovalent interactions; recent years have seen synthetic chemists begin to seriously explore these interactions in catalyst designs that also incorporate a reactive transition metal. In isolation, a single ionic interaction exhibits low directionality, but in many successful systems they exist alongside additional interactions which can provide a high degree of organization at the selectivity-determining transition state. Even in situations with a single key interaction, low directionality is not always detrimental, and can even be advantageous, conferring generality to a single catalyst. This Review explores design approaches that utilize ionic interactions to control selectivity in transition metal catalysis. It is divided into two halves: in the first, the ionic interaction occurs in the outer sphere of the metal complex, using a ligand which is charged or bound to an anion; in the second, the metal bears a formal charge, and the ionic interaction is with an associated counterion.","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"4 1","pages":""},"PeriodicalIF":62.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526020","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}

{"title":"Design Approaches That Utilize Ionic Interactions to Control Selectivity in Transition Metal Catalysis","authors":"Hannah K. Adams,&nbsp;Max Kadarauch,&nbsp;Nicholas J. Hodson,&nbsp;Arthur R. Lit and Robert J. Phipps*,&nbsp;","doi":"10.1021/acs.chemrev.4c0084910.1021/acs.chemrev.4c00849","DOIUrl":"https://doi.org/10.1021/acs.chemrev.4c00849https://doi.org/10.1021/acs.chemrev.4c00849","url":null,"abstract":"<p >The attractive force between two oppositely charged ions can constitute a powerful design tool in selective catalysis. Enzymes make extensive use of ionic interactions alongside a variety of other noncovalent interactions; recent years have seen synthetic chemists begin to seriously explore these interactions in catalyst designs that also incorporate a reactive transition metal. In isolation, a single ionic interaction exhibits low directionality, but in many successful systems they exist alongside additional interactions which can provide a high degree of organization at the selectivity-determining transition state. Even in situations with a single key interaction, low directionality is not always detrimental, and can even be advantageous, conferring generality to a single catalyst. This Review explores design approaches that utilize ionic interactions to control selectivity in transition metal catalysis. It is divided into two halves: in the first, the ionic interaction occurs in the outer sphere of the metal complex, using a ligand which is charged or bound to an anion; in the second, the metal bears a formal charge, and the ionic interaction is with an associated counterion.</p>","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"125 5","pages":"2846–2907 2846–2907"},"PeriodicalIF":51.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrev.4c00849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143590678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction: “Noncanonical Amino Acids”","authors":"Nediljko Budisa*,&nbsp;","doi":"10.1021/acs.chemrev.5c0006510.1021/acs.chemrev.5c00065","DOIUrl":"https://doi.org/10.1021/acs.chemrev.5c00065https://doi.org/10.1021/acs.chemrev.5c00065","url":null,"abstract":"","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"125 4","pages":"1659–1662 1659–1662"},"PeriodicalIF":51.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486915","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}

{"title":"Chemical Design of Magnetic Nanomaterials for Imaging and Ferroptosis-Based Cancer Therapy.","authors":"Wei Xu, Guoqiang Guan, Renye Yue, Zhe Dong, Lingling Lei, Heemin Kang, Guosheng Song","doi":"10.1021/acs.chemrev.4c00546","DOIUrl":"10.1021/acs.chemrev.4c00546","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, its clinical application in oncology is currently limited by issues such as suboptimal efficacy and potential off-target effects. The advent of nanotechnology has provided a new way for overcoming these challenges through the development of activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed to improve the specificity and efficacy of ferroptosis induction. This Review delves into the chemical and biological principles guiding the design of MNPs for ferroptosis-based cancer therapies and imaging-guided therapies. It discusses the regulatory mechanisms and biological attributes of ferroptosis, the chemical composition of MNPs, their mechanism of action as ferroptosis inducers, and their integration with advanced imaging techniques for therapeutic monitoring. Additionally, we examine the convergence of ferroptosis with other therapeutic strategies, including chemodynamic therapy, photothermal therapy, photodynamic therapy, sonodynamic therapy, and immunotherapy, within the context of nanomedicine strategies utilizing MNPs. This Review highlights the potential of these multifunctional MNPs to surpass the limitations of conventional treatments, envisioning a future of drug-resistance-free, precision diagnostics and ferroptosis-based therapies for treating recalcitrant cancers.</p>","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":" ","pages":"1897-1961"},"PeriodicalIF":51.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412272","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}

{"title":"Introduction: “Noncanonical Amino Acids”","authors":"Nediljko Budisa","doi":"10.1021/acs.chemrev.5c00065","DOIUrl":"https://doi.org/10.1021/acs.chemrev.5c00065","url":null,"abstract":"Published as part of &lt;i&gt;Chemical Reviews&lt;/i&gt; special issue “Noncanonical Amino Acids”. Life is a chemically driven process, shaped by Earth’s geology and relying on persistent small molecules for core chemistry, while transient macromolecules control informational, thermodynamic and kinetic functions. Morowitz and Smith (1) have identified 60 universal carbon metabolites, with the central citric acid cycle providing stable intermediates as building blocks for biosynthesis, including proteins. The genetic code has evolved together with metabolism and expanded from a minimal set of amino acids (e.g., the “Alanine World Model” (2) postulates that there were Gly, Pro, Ala and a cationic amino acid) to the extant canonical 20. The special canonical amino acids selenocysteine and pyrrolysine (3) further expand the genetic code in certain life taxa. Wong’s coevolutionary theory (4) states that the code has evolved together with amino acid biosynthesis, starting with prebiotic amino acids and expanding through the reassignment of codons by means of “codon capture” or “ambiguous intermediate” mechanisms. (5) In this special issue on “&lt;i&gt;Noncanonical Amino Acids&lt;/i&gt;”, Tze-Fei Wong builds on his lifelong work on the Co-evolution Theory and presents an excellent article “&lt;i&gt;Triphasic Development of the Genetic Code&lt;/i&gt;” describing three distinct phases in the evolution of the genetic code. Phase 1 is the initial development of the amino acid repertoire in the RNA world. Phase 2 marks the emergence of cells with core metabolic pathways capable of delivering stable intermediates that served as precursors for most canonical amino acids in the extant genetic code. With an eye to the future, Wong anticipates Phase 3, in which the genetic code will expand its amino acid repertoire through anthropogenic intervention (incorporation of noncanonical amino acids (ncAAs)), paving the way for synthetic life forms with brand new genetic codes. The 20 α-L-canonical amino acids encoded by the universal genetic code are translated by ribosomal machinery, including tRNA, aminoacyl-tRNA synthetases (aaRSs), ribosomes, and associated factors. Protein translation decodes amino acid structures from nucleic acid sequences and recodes them into proteins, enabling programmable peptide and protein production. Expansion of the genetic code to incorporate ncAAs presents a significant biochemical challenge and offers insights into information flow, evolutionary innovation, and the possibilities for creating an “orthogonal central dogma” (6) (see Scheme 1) and synthetic cells with alternative life chemistry. (7) This approach enables new therapeutic proteins, biocatalysts for synthetic chemistry, and biological containment strategies. Although the technology has immense academic and industrial potential, much of it still remains untapped. &lt;span&gt;&lt;sup&gt;a&lt;/sup&gt;&lt;/span&gt;This framework comprises two main approaches: designing alternative nucleic acids (Xeno-Nucleic Acids, XNAs) as information po","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":"66 1","pages":""},"PeriodicalIF":62.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496053","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}

{"title":"Strategies to Expand the Genetic Code of Mammalian Cells.","authors":"Arianna O Osgood, Zeyi Huang, Kaitlyn H Szalay, Abhishek Chatterjee","doi":"10.1021/acs.chemrev.4c00730","DOIUrl":"10.1021/acs.chemrev.4c00730","url":null,"abstract":"<p><p>Genetic code expansion (GCE) in mammalian cells has emerged as a powerful technology for investigating and engineering protein function. This method allows for the precise incorporation of a rapidly growing toolbox of noncanonical amino acids (ncAAs) into predefined sites of target proteins expressed in living cells. Due to the minimal size of these genetically encoded ncAAs, the wide range of functionalities they provide, and the ability to introduce them freely at virtually any site of any protein by simple mutagenesis, this technology holds immense potential for probing the complex biology of mammalian cells and engineering next-generation biotherapeutics. In this review, we provide an overview of the underlying machinery that enables ncAA mutagenesis in mammalian cells and how these are developed. We have also compiled an updated list of ncAAs that have been successfully incorporated into proteins in mammalian cells. Finally, we provide our perspectives on the current challenges that need to be addressed to fully harness the potential of this technology.</p>","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":" ","pages":"2474-2501"},"PeriodicalIF":51.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404898","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}