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Approximations of Symbolic Substitution Systems in One Dimension 一维符号替换系统的近似值
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-03-22 DOI: 10.1002/ijch.202300121
Lior Tenenbaum
Periodic approximations of quasicrystals are a powerful tool in analyzing spectra of Schrödinger operators arising from quasicrystals, given the known theory for periodic crystals. Namely, we seek periodic operators whose spectra approximate the spectrum of the limiting operator (of the quasicrystal). This naturally leads to study the convergence of the underlying dynamical systems. We treat dynamical systems which are based on one‐dimensional substitutions. We first find natural candidates of dynamical subsystems to approximate the substitution dynamical system. Subsequently, we offer a characterization of their convergence and provide estimates for the rate of convergence. We apply the proposed theory to some guiding examples.
根据已知的周期晶体理论,准晶体的周期近似是分析由准晶体产生的薛定谔算子谱的有力工具。也就是说,我们要寻找其频谱近似于(准晶体的)极限算子频谱的周期算子。这自然会引出对底层动力系统收敛性的研究。我们处理基于一维置换的动力系统。我们首先找到了近似置换动力系统的自然候选动力子系统。随后,我们对它们的收敛性进行了描述,并提供了收敛速率的估计值。我们将提出的理论应用于一些指导性实例。
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引用次数: 0
Non‐Canonical Amino Acids for Engineering Peptides and Proteins with new Functions 用于制造具有新功能的多肽和蛋白质的非标准氨基酸
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-03-21 DOI: 10.1002/ijch.202400006
Kelly Zhi Qi Zhou, Richard Obexer
The universal genetic code, which specifies the 20 standard amino acids (AAs), forms the basis for all natural proteins. Researchers have developed efficient and robust in vivo and in vitro strategies to overcome the constraints of the genetic code to expand the repertoire of AA building blocks that can be ribosomally incorporated into proteins. This review summarizes the development of these in vivo and in vitro systems and their subsequent use for engineering of peptides and proteins with new functions. In vivo genetic code expansion employing engineered othogonal tRNA/aaRS pairs has led to the development of proteins that selectively bind small molecules, cleave nucleic acids and catalyze non‐natural chemical transformations. In vitro genetic code reprogramming using Flexizymes coupled with mRNA display has resulted in potent macrocyclic peptides that selectively bind to therapeutically important proteins. Through these examples, we hope to illustrate how genetic code expansion and reprogramming, especially when coupled with directed evolution or in vitro selection techniques, have emerged as powerful tools for expanding the functional capabilities of peptides and proteins.
通用遗传密码规定了 20 种标准氨基酸 (AA),是所有天然蛋白质的基础。研究人员已经开发出高效、稳健的体内和体外策略,以克服遗传密码的限制,扩大可通过核糖体合成蛋白质的 AA 构建模块的范围。本综述总结了这些体内和体外系统的开发及其在具有新功能的多肽和蛋白质工程中的后续应用。体内遗传密码扩增采用了工程化的非对称 tRNA/aaRS 对,开发出了可选择性结合小分子、裂解核酸和催化非天然化学转化的蛋白质。利用 Flexizymes 和 mRNA 显示技术进行体外遗传密码重编程,开发出了选择性结合重要治疗蛋白的强效大环肽。通过这些例子,我们希望说明遗传密码扩展和重编程,尤其是与定向进化或体外选择技术相结合时,是如何成为扩展多肽和蛋白质功能的强大工具的。
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引用次数: 0
Recent Advances in Non‐Standard Macrocyclic Peptide Ligand Discovery using mRNA Display 利用 mRNA 显示发现非标准大环肽配体的最新进展
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-03-13 DOI: 10.1002/ijch.202300167
Yizhen Yin, Christopher John Hipolito
Advancements in platform technologies have facilitated the production of libraries consisting of macrocyclic peptides composed of natural and non‐canonical amino acids for more drug‐like characteristics. Identification of macrocyclic peptide ligands against targets of interest can be accomplished using mRNA display. Despite numerous successful in vitro selections for macrocyclic peptide ligands against extracellular targets, identifying macrocyclic peptide hits that can reach intracellular targets continue to be a challenge. Breakthroughs in defining the features of a macrocyclic peptide that promote cell permeability have recently been disclosed. Here, we review the successful selections of non‐standard macrocyclic peptide ligands using mRNA display in the last five years and chemical optimization of a drug‐like macrocyclic peptide ligand for targeting intracellular KRAS.
平台技术的进步促进了由天然和非典型氨基酸组成的大环肽库的生产,使其具有更多类似药物的特性。利用 mRNA 显示技术,可以识别针对感兴趣靶点的大环肽配体。尽管体外筛选针对细胞外靶点的大环肽配体取得了许多成功,但识别能到达细胞内靶点的大环肽仍然是一项挑战。最近,在确定促进细胞渗透性的大环肽特征方面取得了突破性进展。在此,我们回顾了过去五年中利用 mRNA 展示成功筛选出的非标准大环肽配体,以及针对细胞内 KRAS 的类药物大环肽配体的化学优化。
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引用次数: 0
Modulating the Acceptor Preference of His‐C‐Geranyltransferase LimF 调节 His-C-Geranyl 转移酶 LimF 的受体偏好
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-03-12 DOI: 10.1002/ijch.202300182
Yuchen Zhang, Yuki Goto, Hiroaki Suga
Lipidation stands as a pivotal strategy for enhancing the metabolic stability of target peptides. Prenyltransferases in cyanobactin biosynthesis have garnered significant attention as potential peptide lipidation biocatalysts because of their exceptional regio‐ and chemoselectivity. However, these enzymes often exhibit a biased preference for certain acceptor substrates, requiring specific amino acids adjacent to the modifying residue. In this study, we demonstrate the structure‐guided engineering of LimF, a His‐C‐geranyltransferase, to broaden its peptide substrate tolerance. By altering key residues in the peptide‐binding pocket, we created a LimF variant capable of modifying sequence motifs previously inaccessible to the wildtype enzyme. The variant successfully modified some previously unfavored sequence motifs in artificial peptide substrates and bioactive peptide agents, validating the engineered substrate scope. With the discovery of novel peptide prenyltransferases, this approach would lead to a more comprehensive toolbox of peptide prenylation biocatalysts.
脂化是提高目标肽代谢稳定性的关键策略。作为潜在的肽脂化生物催化剂,蓝藻生物合成中的异戊烯基转移酶因其卓越的区域和化学选择性而备受关注。然而,这些酶通常对某些接受底物表现出偏好性,需要与修饰残基相邻的特定氨基酸。在本研究中,我们展示了在结构指导下对 His-C-geranyl 转化酶 LimF 进行的工程改造,以拓宽其对肽底物的耐受性。通过改变肽结合口袋中的关键残基,我们创造了一种 LimF 变体,它能够修饰野生型酶以前无法访问的序列基团。该变体成功地修饰了人工肽底物和生物活性肽制剂中一些以前不喜欢的序列基团,验证了工程底物的范围。随着新型肽前酰转移酶的发现,这种方法将带来更全面的肽前酰化生物催化剂工具箱。
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引用次数: 0
The Transthyretin Protein and Amyloidosis – an Extraordinary Chemical Biology Platform 转甲状腺素蛋白与淀粉样变性--非同寻常的化学生物学平台
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-03-06 DOI: 10.1002/ijch.202300164
Per Hammarström
The amyloidoses are diseases caused by accumulation of amyloid fibrils from over 40 different human misfolded proteins in various organs of the body depending on precursor protein. Amyloidogenesis is a self‐perpetuating reaction with deleterious consequences causing degeneration in cells and organs where depositions occur. Transthyretin, TTR, is an amyloidogenic protein causing sporadic disease from the wild‐type protein during aging and from numerous different autosomal dominant familial mutations at earlier ages depending on the sequence of the hereditary variant. Until recently the disease process was poorly understood, and therapies were scarce. Over the past decades, spurred by clinical data, using chemical biology research, the mechanisms of TTR production and misfolding have been elucidated affording almost complete coverage of the TTR amyloidogenesis pathway to be targeted. This translational science success has provided a plethora of therapeutic options for the TTR amyloidoses providing an inspiring example for success in previously intractable diseases.
淀粉样蛋白病是由 40 多种不同的人类错误折叠蛋白的淀粉样蛋白纤维在人体各器官中积聚而引起的疾病,具体情况取决于前体蛋白。淀粉样蛋白的生成是一种自我延续的反应,会造成有害后果,导致发生沉积的细胞和器官变性。Transthyretin(TTR)是一种淀粉样蛋白生成蛋白,野生型蛋白在衰老过程中会导致散发性疾病,而众多不同的常染色体显性家族突变则会根据遗传变异的序列在较早年龄段导致疾病。直到最近,人们对这种疾病的发病过程还知之甚少,治疗方法也十分匮乏。过去几十年来,在临床数据的推动下,利用化学生物学研究,TTR 生成和错误折叠的机制已被阐明,从而几乎完全覆盖了 TTR 淀粉样蛋白生成途径。这一转化科学成果为 TTR 淀粉样蛋白病提供了大量治疗方案,为以往难以治愈的疾病提供了成功的范例。
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引用次数: 0
Deamination- or N-Nitrosation-Based Methods for m6A Profiling 基于脱氨基或 N-亚硝基的 m6A 分析方法
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-03-04 DOI: 10.1002/ijch.202300180
Weiguo Shen, Jing Wang

The addition of various chemical modifications to RNA introduces an additional layer of complexity to the regulation of gene expression. Among all RNA modifications, N6-methyladenosine (m6A) has earned its status as the most abundant and well-studied post-transcriptional modification in mammalian mRNA. Nevertheless, understanding the role of m6A in shaping the fate of RNA molecules and its influence on gene expression heavily depends on the development and application of detection technologies. Among all m6A detection methods, chemical-based sequencing methods show unique advantages. Our group recently developed an absolute quantification method named GLORI, which employs nitrite and glyoxal to convert adenosine to inosine efficiently. With its potential to emerge as the gold standard for m6A detection, GLORI showcases the promise of nitrite-based approaches. This review provides a comprehensive overview of m6A detection techniques based on deamination or nitrosation, evaluating their strengths and limitations. Furthermore, we offer insights into the future directions of innovative approaches in m6A profiling.

在 RNA 上添加各种化学修饰会给基因表达调控带来额外的复杂性。在所有 RNA 修饰中,N6-甲基腺苷(m6A)是哺乳动物 mRNA 中含量最多、研究最深入的转录后修饰。然而,要了解 m6A 在塑造 RNA 分子命运中的作用及其对基因表达的影响,在很大程度上取决于检测技术的开发和应用。在所有 m6A 检测方法中,基于化学的测序方法显示出独特的优势。我们小组最近开发了一种名为 GLORI 的绝对定量方法,它利用亚硝酸盐和乙二醛将腺苷有效地转化为肌苷。GLORI 有可能成为 m6A 检测的黄金标准,它展示了基于亚硝酸盐方法的前景。本综述全面概述了基于脱氨或亚硝基化的 m6A 检测技术,评估了它们的优势和局限性。此外,我们还对 m6A 图谱分析创新方法的未来发展方向提出了见解。
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引用次数: 0
RNA-Guided RNA Pseudouridylation and 2’-O-Methylation RNA 引导的 RNA 伪尿苷化和 2'-O 甲基化
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-02-27 DOI: 10.1002/ijch.202400005
Hironori Adachi, Jonathan L. Chen, W.-Matthias Leeder, Pedro Morais, Yi-Tao Yu

RNA-guided RNA modifications, including pseudouridylation and 2′-O-methylation, are naturally occurring processes that introduce pseudouridines (Ψ) and 2’-O-methylated residues (2’-O−Me) into various types of RNA. This modification is orchestrated by two distinct families of ribonucleoprotein complexes: Box H/ACA RNP and Box C/D RNP. Each complex comprises a unique guide (g)RNA (Box H/ACA gRNA or Box C/D gRNA) and a set of core proteins responsible for pseudouridylation and 2’-O-methylation, respectively. The specificity of these modifications is conferred by base-pairing of Box H/ACA gRNA and Box C/D gRNA with their RNA substrates. Here, we discuss the mechanism and function of RNA-guided pseudouridylation and 2’-O-methylation.

RNA 引导的 RNA 修饰(包括假核苷酸化和 2′-O-甲基化)是将假核苷酸(Ψ)和 2'-O 甲基化残基(2'-O-Me)引入各类 RNA 的自然发生过程。这种修饰是由两个不同的核糖核蛋白复合物家族协调进行的:盒 H/ACA RNP 和盒 C/D RNP。每个复合体都由一个独特的引导(g)RNA(Box H/ACA gRNA 或 Box C/D gRNA)和一组分别负责假酰化和 2'-O-甲基化的核心蛋白组成。盒 H/ACA gRNA 和盒 C/D gRNA 与其 RNA 底物的碱基配对赋予了这些修饰的特异性。在此,我们将讨论 RNA 引导的假酸化和 2'-O- 甲基化的机制和功能。
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引用次数: 0
Cover Picture: (Isr. J. Chem. 1-2/2024) 封面图片:(Isr.)
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-02-26 DOI: 10.1002/ijch.202480101

The cover picture shows a cyclic voltammogram and catalytically active intermediates, highlighting the importance of a rationale for innovations in the rapidly evolving field of molecular electrosynthesis. Also, as a product structure, a C7 substituted indole, derived through electrocatalysis, is depicted.

封面图片显示的是循环伏安图和催化活性中间体,突出了在快速发展的分子电合成领域创新原理的重要性。此外,还展示了通过电催化得到的 C7 取代吲哚的产品结构。
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引用次数: 0
Cellular Metabolic Labeling of Nucleic Acids and Its Applications 核酸的细胞代谢标记及其应用
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-02-23 DOI: 10.1002/ijch.202300165
Dr. Zhiyong He, Prof. Xiang Zhou

Nucleic acids are considered as fundamental molecules of living systems, which serve as universal genetic information messengers and repositories. To uncover the multifaceted aspects of nucleic acid function and metabolism within cells, labeling has become indispensable. This labeling technique enables the visualization, isolation, characterization, and even quantification of specific nucleic acid species. This review delves into cellular metabolic approaches for nucleic acid labeling, wherein enzymatic steps are employed to introduce nucleic acid modifications before conjugation with a label for detection or isolation. The discussion begins with metabolic labeling for DNA, RNA with various reactive groups and post-transcriptional RNA labeling for RNA methylation and acetylation sites, emphasizing recent advancements in the field and then, we spotlighted pertinent applications for cellular imaging and sequencing. of labeling.

核酸被认为是生命系统的基本分子,是通用的遗传信息信使和储存库。要揭示细胞内核酸功能和新陈代谢的方方面面,标记技术已变得不可或缺。这种标记技术可实现特定核酸种类的可视化、分离、表征甚至量化。本综述深入探讨了核酸标记的细胞代谢方法,其中采用酶步骤引入核酸修饰,然后再与标记物连接进行检测或分离。讨论从 DNA 的代谢标记、带有各种活性基团的 RNA 标记以及转录后 RNA 甲基化和乙酰化位点的 RNA 标记开始,强调了该领域的最新进展,然后重点介绍了细胞成像和测序的相关应用。
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引用次数: 0
Special Issue on Electrochemically-Driven Organic Synthesis 电化学驱动的有机合成特刊
IF 3.2 4区 化学 Q2 Chemistry Pub Date : 2024-02-22 DOI: 10.1002/ijch.202400022
Prof. Dr. Lutz Ackermann

Molecular synthesis has gained considerable momentum through the impetus provided by electrochemically-enabled redox manipulation.1 Organic electrosynthesis and electrocatalysis bear a unique potential to substantially improve molecular chemistry and provide a wide range of innovative transformations. While a first electrochemically-driven organic synthesis dates back to Kolbe's decarboxylative homocoupling in 1848,2 organic electrosynthesis has remained largely underexplored. Particularly, recent years have witnessed a remarkable renaissance of electrochemically-enabled organic reactions. Pioneering contributions have during the past several years illustrated the unique opportunities that electrochemistry offers for the assembly of novel molecular structures, while improving the efficiency and sustainability of molecular synthesis. In this Special Issue, the Israelian Journal of Chemistry highlights the latest progress in this field.

Articles enclosed in this Special Issue cover overviews of important recent achievements in electrochemically driven organic synthesis as well as important original research articles on molecular organic electrosynthesis. Thus, Xu reviewed strategies that exploit ferrocene as redox catalyst, emphasizing the power towards catalyzed radical formation.3 Likewise, Onomura summarized the potential of halogen mediators for environmentally-benign and at the same time efficient alcohol oxidations.4 Jiao and Mei showed the power of paired electrolysis for organic reactions with ideal resource-economy,5 while Cheng outlined the challenges and benefits of water as a particularly benign reaction medium.6 Besides electrooxidative strategies, electroreductive transformations have garnered major recent attention. In this context, Weix summarized electrochemical nickel-catalyzed C−C bond formations through cross-electrophile coupling,7 while Gosmini provided an overview on powerful transition metal-catalyzed electroreductive approachess for C−C bond formation.8 On a different note, de Sarkar focused on electroreductive transformations involving C−C and C−O multiple bonds.9 Novel innovative concepts in the realm of organic electrosynthesis, are presented in selected research articles highlighting exciting recent advances. Here, Ruan established an electrochemical cascade cyclization for a convenient access to 3-selenylindoles,10 while Ackermann established C7-indole alkenylations based on rhodaelectrocatalysis.11 The elegant design of an off/on switching enabled Kakiuchi to establish a one-pot cross-coupling/C−H bromination for bromoarylpyridines.12 Finally, Fuchigami systematically compared the impact of the anode materials on the pe

1 有机电合成和电催化在大幅改进分子化学和提供广泛的创新转化方面具有独特的潜力。虽然最早的电化学驱动有机合成可追溯到 1848 年 Kolbe 的脱羧同偶联反应2 ,但有机电合成在很大程度上仍未得到充分探索。特别是近年来,电化学驱动的有机反应出现了显著的复兴。过去几年中,一些开创性的研究成果表明,电化学为组装新型分子结构提供了独特的机会,同时提高了分子合成的效率和可持续性。在本特刊中,《以色列化学杂志》重点介绍了这一领域的最新进展。本特刊收录的文章包括电化学驱动有机合成领域最新重要成就的概述,以及有关分子有机电合成的重要原创研究文章。因此,Xu 综述了利用二茂铁作为氧化还原催化剂的策略,强调了催化自由基形成的威力。3 同样,Onomura 总结了卤素介质在环境无害同时高效的醇氧化中的潜力。在这方面,Weix 总结了通过交叉亲电偶联的电化学镍催化 C-C 键形成7,而 Gosmini 则概述了强大的过渡金属催化 C-C 键形成的电还原方法8。其中,Ruan 建立了一种电化学级联环化方法,可方便地获得 3-硒基吲哚10,而 Ackermann 则建立了基于 rhodaelectrocatalysis 的 C7-indole 烯化反应11。最后,Fuchigami 系统地比较了阳极材料对各种阳极转化性能的影响。13 © WSS, Felix Wey总之,本特刊反映了有机电化学领域的巨大进步,来自美国、欧洲和亚洲的该领域世界领先的从业人员做出了杰出贡献,反映了利用电力实现可持续未来的国际重要性。电化学有机合成具有直接促进实现联合国众多可持续发展目标14 的潜力,包括 "良好的健康和福祉"、"负担得起的清洁能源"、"工业、创新和基础设施"、"负责任的消费和生产 "以及 "气候行动 "等目标。同时,电化学的统一影响涉及到绿色化学的所有十二项原则15。总体而言,电化学分子合成已被公认为有机化学家独一无二的强大平台。鉴于有机电化学在有机分子的可持续组装方面具有突出的创新潜力,预计这一快速发展的研究领 域将取得各种令人振奋的进展。
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引用次数: 0
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Israel Journal of Chemistry
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