Pub Date : 2024-09-23DOI: 10.1038/s41570-024-00654-7
Sihan Xiong, Khalid Shah, Chuang Liu
An mRNA sequence that encodes a zwitterionic polypeptide fused to a therapeutic protein improves the pharmacokinetic properties of mRNA therapeutics.
编码与治疗蛋白融合的齐聚物多肽的 mRNA 序列可改善 mRNA 疗法的药代动力学特性。
{"title":"A zwitterionic twist","authors":"Sihan Xiong, Khalid Shah, Chuang Liu","doi":"10.1038/s41570-024-00654-7","DOIUrl":"10.1038/s41570-024-00654-7","url":null,"abstract":"An mRNA sequence that encodes a zwitterionic polypeptide fused to a therapeutic protein improves the pharmacokinetic properties of mRNA therapeutics.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"721-721"},"PeriodicalIF":38.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276706","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}
Pub Date : 2024-09-20DOI: 10.1038/s41570-024-00653-8
Glenn A. Hurst
Strong partnerships with students are critical to curriculum development and research. This can foster a culture of continual improvement with educational and societal benefit.
{"title":"Student partnerships for sustainable change","authors":"Glenn A. Hurst","doi":"10.1038/s41570-024-00653-8","DOIUrl":"10.1038/s41570-024-00653-8","url":null,"abstract":"Strong partnerships with students are critical to curriculum development and research. This can foster a culture of continual improvement with educational and societal benefit.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"717-718"},"PeriodicalIF":38.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276791","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}
Pub Date : 2024-09-09DOI: 10.1038/s41570-024-00647-6
Arismel Tena Meza, Laura G. Wonilowicz, Neil K. Garg
Chem Kids is a science camp where children ages 10 to 12 years old learn the notoriously difficult subject of organic chemistry.
Chem Kids 是一个科学夏令营，让 10 至 12 岁的儿童学习众所周知的有机化学难点。
{"title":"Organic chemistry for kids","authors":"Arismel Tena Meza, Laura G. Wonilowicz, Neil K. Garg","doi":"10.1038/s41570-024-00647-6","DOIUrl":"10.1038/s41570-024-00647-6","url":null,"abstract":"Chem Kids is a science camp where children ages 10 to 12 years old learn the notoriously difficult subject of organic chemistry.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"715-716"},"PeriodicalIF":38.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160381","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}
Pub Date : 2024-09-09DOI: 10.1038/s41570-024-00645-8
Brandon A. Wright, Richmond Sarpong
The generation of molecular complexity is a primary goal in the field of synthetic chemistry. In the context of retrosynthetic analysis, the concept of molecular complexity is central to identifying productive disconnections and the development of efficient total syntheses. However, this field-defining concept is frequently invoked on an intuitive basis without precise definition or appreciation of its subtleties. Methods for quantifying molecular complexity could prove useful for characterizing the state of synthesis in a more rigorous, reliable and reproducible fashion. As a first step to evaluating the importance of these methods to the state of the field, here we present our perspective on the development of molecular complexity quantification and its implications for chemical synthesis. The extension and application of these methods beyond computer-aided synthesis planning and medicinal chemistry to the traditional practice of ‘complex molecule’ synthesis could have the potential to unearth new opportunities and more efficient approaches for synthesis. Quantifying molecular complexity has the potential to enhance retrosynthetic analysis and, thus, aid the development of efficient total syntheses. This Perspective discusses methods for rigorous, reproducible complexity measurement, highlighting their potential to revolutionize traditional complex molecule synthesis and uncover new synthetic opportunities.
{"title":"Molecular complexity as a driving force for the advancement of organic synthesis","authors":"Brandon A. Wright, Richmond Sarpong","doi":"10.1038/s41570-024-00645-8","DOIUrl":"10.1038/s41570-024-00645-8","url":null,"abstract":"The generation of molecular complexity is a primary goal in the field of synthetic chemistry. In the context of retrosynthetic analysis, the concept of molecular complexity is central to identifying productive disconnections and the development of efficient total syntheses. However, this field-defining concept is frequently invoked on an intuitive basis without precise definition or appreciation of its subtleties. Methods for quantifying molecular complexity could prove useful for characterizing the state of synthesis in a more rigorous, reliable and reproducible fashion. As a first step to evaluating the importance of these methods to the state of the field, here we present our perspective on the development of molecular complexity quantification and its implications for chemical synthesis. The extension and application of these methods beyond computer-aided synthesis planning and medicinal chemistry to the traditional practice of ‘complex molecule’ synthesis could have the potential to unearth new opportunities and more efficient approaches for synthesis. Quantifying molecular complexity has the potential to enhance retrosynthetic analysis and, thus, aid the development of efficient total syntheses. This Perspective discusses methods for rigorous, reproducible complexity measurement, highlighting their potential to revolutionize traditional complex molecule synthesis and uncover new synthetic opportunities.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"776-792"},"PeriodicalIF":38.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160386","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}
Pub Date : 2024-09-02DOI: 10.1038/s41570-024-00646-7
Saman Fatima, Lisa Olshansky
From the reduction of dinitrogen to the oxidation of water, the chemical transformations catalysed by metalloenzymes underlie global geochemical and biochemical cycles. These reactions represent some of the most kinetically and thermodynamically challenging processes known and require the complex choreography of the fundamental building blocks of nature, electrons and protons, to be carried out with utmost precision and accuracy. The rate-determining step of catalysis in many metalloenzymes consists of a protein structural rearrangement, suggesting that nature has evolved to leverage macroscopic changes in protein molecular structure to control subatomic changes in metallocofactor electronic structure. The proton-coupled electron transfer mechanisms operative in nitrogenase, photosystem II and ribonucleotide reductase exemplify this interplay between molecular and electronic structural control. We present the culmination of decades of study on each of these systems and clarify what is known regarding the interplay between structural changes and functional outcomes in these metalloenzyme linchpins. Rate-limiting conformational changes often gate the formation of catalytically active metalloenzyme states. We review examples of the interplay between macroscopic changes in protein molecular structure and subatomic changes in metallocofactor electronic structure that together enable precision control over nature’s redox machines.
从二氮的还原到水的氧化，金属酶催化的化学变化是全球地球化学和生物化学循环的基础。这些反应是已知的动力学和热力学上最具挑战性的过程，需要对自然界的基本组成单元--电子和质子--进行复杂的编排，以达到最高的精确度和准确性。许多金属酶催化作用的决定速率步骤包括蛋白质结构的重新排列，这表明大自然已经进化到可以利用蛋白质分子结构的宏观变化来控制金属因子电子结构的亚原子变化。氮化酶、光系统 II 和核糖核苷酸还原酶中的质子耦合电子传递机制就是分子结构和电子结构控制之间相互作用的例证。我们介绍了数十年来对上述每个系统的研究成果，并阐明了这些金属酶连接蛋白的结构变化与功能结果之间的相互作用。
{"title":"Conformational control over proton-coupled electron transfer in metalloenzymes","authors":"Saman Fatima, Lisa Olshansky","doi":"10.1038/s41570-024-00646-7","DOIUrl":"10.1038/s41570-024-00646-7","url":null,"abstract":"From the reduction of dinitrogen to the oxidation of water, the chemical transformations catalysed by metalloenzymes underlie global geochemical and biochemical cycles. These reactions represent some of the most kinetically and thermodynamically challenging processes known and require the complex choreography of the fundamental building blocks of nature, electrons and protons, to be carried out with utmost precision and accuracy. The rate-determining step of catalysis in many metalloenzymes consists of a protein structural rearrangement, suggesting that nature has evolved to leverage macroscopic changes in protein molecular structure to control subatomic changes in metallocofactor electronic structure. The proton-coupled electron transfer mechanisms operative in nitrogenase, photosystem II and ribonucleotide reductase exemplify this interplay between molecular and electronic structural control. We present the culmination of decades of study on each of these systems and clarify what is known regarding the interplay between structural changes and functional outcomes in these metalloenzyme linchpins. Rate-limiting conformational changes often gate the formation of catalytically active metalloenzyme states. We review examples of the interplay between macroscopic changes in protein molecular structure and subatomic changes in metallocofactor electronic structure that together enable precision control over nature’s redox machines.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"762-775"},"PeriodicalIF":38.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120237","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}
Pub Date : 2024-08-23DOI: 10.1038/s41570-024-00640-z
Abhishek Singh, Payel Parvin, Bapan Saha, Dibyendu Das
The soft and wet machines of life emerged as the spatially enclosed ensemble of biomolecules with replicating capabilities integrated with metabolic reaction cycles that operate at far-from-equilibrium. A thorough step-by-step synthetic integration of these elements, namely metabolic and replicative properties all confined and operating far-from-equilibrium, can set the stage from which we can ask questions related to the construction of chemical-based evolving systems with living matter-like properties — a monumental endeavour of systems chemistry. The overarching concept of this Review maps the discoveries on this possible integration of reaction networks, self-reproduction and compartmentalization under non-equilibrium conditions. We deconvolute the events of reaction networks and transient compartmentalization and extend the discussion towards self-reproducing systems that can be sustained under non-equilibrium conditions. Although enormous challenges lie ahead in terms of molecular diversity, information transfer, adaptation and selection that are required for open-ended evolution, emerging strategies to generate minimal metabolic cycles can extend our growing understanding of the chemical emergence of the biosphere of Earth. The origins of complex life forms from simple chemicals remain one of the most enigmatic mysteries. This Review explores how non-equilibrium chemical-based systems can exhibit living matter-like properties with an outlook that connects the possibility of diversification, adaptation and evolution.
{"title":"Non-equilibrium self-assembly for living matter-like properties","authors":"Abhishek Singh, Payel Parvin, Bapan Saha, Dibyendu Das","doi":"10.1038/s41570-024-00640-z","DOIUrl":"10.1038/s41570-024-00640-z","url":null,"abstract":"The soft and wet machines of life emerged as the spatially enclosed ensemble of biomolecules with replicating capabilities integrated with metabolic reaction cycles that operate at far-from-equilibrium. A thorough step-by-step synthetic integration of these elements, namely metabolic and replicative properties all confined and operating far-from-equilibrium, can set the stage from which we can ask questions related to the construction of chemical-based evolving systems with living matter-like properties — a monumental endeavour of systems chemistry. The overarching concept of this Review maps the discoveries on this possible integration of reaction networks, self-reproduction and compartmentalization under non-equilibrium conditions. We deconvolute the events of reaction networks and transient compartmentalization and extend the discussion towards self-reproducing systems that can be sustained under non-equilibrium conditions. Although enormous challenges lie ahead in terms of molecular diversity, information transfer, adaptation and selection that are required for open-ended evolution, emerging strategies to generate minimal metabolic cycles can extend our growing understanding of the chemical emergence of the biosphere of Earth. The origins of complex life forms from simple chemicals remain one of the most enigmatic mysteries. This Review explores how non-equilibrium chemical-based systems can exhibit living matter-like properties with an outlook that connects the possibility of diversification, adaptation and evolution.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"723-740"},"PeriodicalIF":38.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045632","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}
Pub Date : 2024-08-22DOI: 10.1038/s41570-024-00641-y
Nikolas Kaltsoyannis, Andrew Kerridge
One of the most intensely studied areas of f-block chemistry is the nature of the bonds between the f-element and another species, and in particular the role played by covalency. Computational quantum chemical methods have been at the forefront of this research for decades and have a particularly valuable role, given the radioactivity of the actinide series. The very strong agreement that has recently emerged between theory and the results of a range of spectroscopic techniques not only facilitates deeper insight into the experimental data, but it also provides confidence in the conclusions from the computational studies. These synergies are shining new light on the nature of the f element–other element bond. We describe recent advances in the understanding of covalency in the f element–other element bond through the synergistic application of computational quantum chemistry with nuclear magnetic resonance and X-ray spectroscopies.
f 嵌段化学研究最深入的领域之一是 f 元素与另一种物质之间的键的性质，特别是共价作用。几十年来，计算量子化学方法一直处于这一研究的前沿，鉴于锕系元素的放射性，这种方法的作用尤为重要。最近，理论与一系列光谱技术的结果之间出现了很强的一致性，这不仅有助于深入了解实验数据，还为计算研究的结论提供了信心。这些协同作用正在揭示 f 元素与其他元素键的本质。
{"title":"Understanding covalency in molecular f-block compounds from the synergy of spectroscopy and quantum chemistry","authors":"Nikolas Kaltsoyannis, Andrew Kerridge","doi":"10.1038/s41570-024-00641-y","DOIUrl":"10.1038/s41570-024-00641-y","url":null,"abstract":"One of the most intensely studied areas of f-block chemistry is the nature of the bonds between the f-element and another species, and in particular the role played by covalency. Computational quantum chemical methods have been at the forefront of this research for decades and have a particularly valuable role, given the radioactivity of the actinide series. The very strong agreement that has recently emerged between theory and the results of a range of spectroscopic techniques not only facilitates deeper insight into the experimental data, but it also provides confidence in the conclusions from the computational studies. These synergies are shining new light on the nature of the f element–other element bond. We describe recent advances in the understanding of covalency in the f element–other element bond through the synergistic application of computational quantum chemistry with nuclear magnetic resonance and X-ray spectroscopies.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 9","pages":"701-712"},"PeriodicalIF":38.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142022275","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}
Pub Date : 2024-08-19DOI: 10.1038/s41570-024-00643-w
Subhajit Dutta
Okra505 is a new green-fluorescent photostable RNA aptamer that enables mRNA dynamics to be visualized in live cellular processes, outperforming established fluorescent RNA visualization tools.
{"title":"Watching RNA in action with a green lantern","authors":"Subhajit Dutta","doi":"10.1038/s41570-024-00643-w","DOIUrl":"10.1038/s41570-024-00643-w","url":null,"abstract":"Okra505 is a new green-fluorescent photostable RNA aptamer that enables mRNA dynamics to be visualized in live cellular processes, outperforming established fluorescent RNA visualization tools.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 9","pages":"651-651"},"PeriodicalIF":38.1,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004849","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}
Pub Date : 2024-08-12DOI: 10.1038/s41570-024-00635-w
Brent S. Visser, Wojciech P. Lipiński, Evan Spruijt
There is an increasing amount of evidence that biomolecular condensates are linked to neurodegenerative diseases associated with protein aggregation, such as Alzheimer’s disease and amyotrophic lateral sclerosis, although the mechanisms underlying this link remain elusive. In this Review, we summarize the possible connections between condensates and protein aggregation. We consider both liquid-to-solid transitions of phase-separated proteins and the partitioning of proteins into host condensates. We distinguish five key factors by which the physical and chemical environment of a condensate can influence protein aggregation, and we discuss their relevance in studies of protein aggregation in the presence of biomolecular condensates: increasing the local concentration of proteins, providing a distinct chemical microenvironment, introducing an interface wherein proteins can localize, changing the energy landscape of aggregation pathways, and the presence of chaperones in condensates. Analysing the role of biomolecular condensates in protein aggregation may be essential for a full understanding of amyloid formation and offers a new perspective that can help in developing new therapeutic strategies for the prevention and treatment of neurodegenerative diseases. Biomolecular condensates help organize cell components under normal conditions but can also be involved in pathological protein aggregation when condensate proteins carry mutations or under stress conditions. This Review discusses the possible mechanisms behind such aggregation processes that potentially lead to neurodegenerative diseases.
{"title":"The role of biomolecular condensates in protein aggregation","authors":"Brent S. Visser, Wojciech P. Lipiński, Evan Spruijt","doi":"10.1038/s41570-024-00635-w","DOIUrl":"10.1038/s41570-024-00635-w","url":null,"abstract":"There is an increasing amount of evidence that biomolecular condensates are linked to neurodegenerative diseases associated with protein aggregation, such as Alzheimer’s disease and amyotrophic lateral sclerosis, although the mechanisms underlying this link remain elusive. In this Review, we summarize the possible connections between condensates and protein aggregation. We consider both liquid-to-solid transitions of phase-separated proteins and the partitioning of proteins into host condensates. We distinguish five key factors by which the physical and chemical environment of a condensate can influence protein aggregation, and we discuss their relevance in studies of protein aggregation in the presence of biomolecular condensates: increasing the local concentration of proteins, providing a distinct chemical microenvironment, introducing an interface wherein proteins can localize, changing the energy landscape of aggregation pathways, and the presence of chaperones in condensates. Analysing the role of biomolecular condensates in protein aggregation may be essential for a full understanding of amyloid formation and offers a new perspective that can help in developing new therapeutic strategies for the prevention and treatment of neurodegenerative diseases. Biomolecular condensates help organize cell components under normal conditions but can also be involved in pathological protein aggregation when condensate proteins carry mutations or under stress conditions. This Review discusses the possible mechanisms behind such aggregation processes that potentially lead to neurodegenerative diseases.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 9","pages":"686-700"},"PeriodicalIF":38.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971451","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":"Stemming the scientific brain drain in Nepal","authors":"Sushila Maharjan, Stephanie Greed","doi":"10.1038/s41570-024-00638-7","DOIUrl":"10.1038/s41570-024-00638-7","url":null,"abstract":"Sushila Maharjan is a biochemist and bioengineer and co-founder of Nepal’s Research Institute for Bioscience and Biotechnology (RIBB).","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 9","pages":"647-648"},"PeriodicalIF":38.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907035","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}
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