Current Opinion in Chemical Biology最新文献

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Corrigendum to “Drug discovery targeting Nav1.8: Structural insights and therapeutic potential” [Curr Opin Chem Biol 83 (2024) 102538] 针对 Nav1.8 的药物发现：结构见解和治疗潜力》[Curr Opin Chem Biol 83 (2024) 102538] 更正

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-11-25 DOI: 10.1016/j.cbpa.2024.102546

Huan Wang , Jian Huang , Jie Zang , Xueqin Jin , Nieng Yan

引用次数: 0

Engineered metallobiocatalysts for energy–relevant reactions 用于能源相关反应的工程金属生物催化剂

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-11-25 DOI: 10.1016/j.cbpa.2024.102545

Ryan M. Kosko , Kaye L. Kuphal , Alison A. Salamatian , Kara L. Bren

Engineering metallobiocatalysts is a promising approach to addressing challenges in energy-relevant electrocatalysis and photocatalysis. The design freedom provided by semisynthetic and fully synthetic approaches to catalyst design allows researchers to demonstrate how structural modifications can improve selectivity and activity of biocatalysts. Furthermore, the provision of a superstructure in many metallobiocatalysts facilitates active-site microenvironment engineering. Recurring themes include the role of the biomolecular scaffold in enhancing reactivity in water and catalyst robustness, the impact of the outer sphere on reactivity, and the importance of tuning system components in full system optimization. In this perspective, recent strategies to design and modify novel biocatalysts, understand proton and electron transfer mechanisms, and tune system activity by modifying catalysts and system conditions are highlighted within the field of energy-related catalysis. Opportunities in this field include developing robust structure–function relationships to support approaches to engineering second-sphere interactions and identifying ways to enhance biocatalyst activity over time.

设计金属生物催化剂是应对能源相关电催化和光催化挑战的一种前景广阔的方法。半合成和全合成催化剂设计方法所提供的设计自由度使研究人员能够展示结构修饰如何提高生物催化剂的选择性和活性。此外，许多金属生物催化剂都具有上层结构，这为活性位点微环境工程提供了便利。反复出现的主题包括生物分子支架在提高水中反应性和催化剂稳健性方面的作用、外球对反应性的影响以及在整个系统优化过程中调整系统组分的重要性。从这个角度出发，重点介绍了在能源相关催化领域设计和改造新型生物催化剂、了解质子和电子转移机制以及通过改造催化剂和系统条件来调整系统活性的最新策略。该领域的机遇包括发展稳健的结构-功能关系，以支持第二球相互作用的工程学方法，以及确定随着时间推移增强生物催化剂活性的方法。

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引用次数: 0

Synthetic ion channels in biomembranes 生物膜中的合成离子通道。

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-11-20 DOI: 10.1016/j.cbpa.2024.102544

Ai Kohata , Kazushi Kinbara

Ion transport across cell membranes is crucial in maintaining ion homeostasis in cells. Synthetic molecules that can mimic the functions of natural ion channel proteins would possess great potential as therapeutic agents by promoting apoptosis or interfering with autophagic processes through perturbing the intracellular pH or inducing oxidative and osmotic stresses. However, little is known about the underlying mechanisms in terms of direct correlation between ion transport and biological functions. This review summarizes recent progress in the area of synthetic transmembrane ion transport systems, focusing on the channel type, with an emphasis on their bioapplications as anticancer agents.

离子在细胞膜上的转运是维持细胞离子平衡的关键。能模拟天然离子通道蛋白功能的合成分子通过扰乱细胞内 pH 值或诱导氧化和渗透压力，促进细胞凋亡或干扰自噬过程，具有很大的治疗潜力。然而，人们对离子转运与生物功能直接相关的内在机制知之甚少。本综述总结了合成跨膜离子转运系统领域的最新进展，重点是通道类型，并着重介绍了它们作为抗癌剂的生物应用。

引用次数: 0

Transferring enzyme features to molecular CO2 reduction catalysts 将酶的特性转化为分子二氧化碳还原催化剂。

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-11-15 DOI: 10.1016/j.cbpa.2024.102540

Matthias Huber, Corinna R. Hess

Carbon monoxide dehydrogenases and formate dehydrogenases efficiently catalyze the reduction of CO₂. In both enzymes, CO₂ activation at the metal active site is assisted by proximate amino acids and Fe–S-clusters. Functional features of the enzyme are mimicked in molecular catalysts by redox-active ligands, acidic and charged groups in the ligand periphery, and binuclear scaffolds. These components have all improved the catalytic performance of synthetic systems. Recent studies impart a deeper understanding of the individual contributions of the various functionalities to reactivity and of their combined effects. New catalyst platforms reveal alternate pathways for CO₂ reduction, unique intermediates, and strategies for switching selectivity. Design of a wider array of complexes that combine different functional elements is encouraged to further optimize catalysts for CO₂ reduction, especially for product formation beyond CO. More diverse bimetallic catalysts are needed to better exploit metal–metal interactions for CO₂ conversion.

一氧化碳脱氢酶和甲酸脱氢酶能有效催化二氧化碳还原。在这两种酶中，金属活性位点上的二氧化碳活化都得到了近似氨基酸和 Fe-S 簇的协助。在分子催化剂中，氧化还原活性配体、配体外围的酸性和带电基团以及双核支架可模拟酶的功能特征。这些成分都提高了合成系统的催化性能。最近的研究加深了人们对各种官能团对反应性的单独贡献及其综合效应的理解。新的催化剂平台揭示了二氧化碳还原的替代途径、独特的中间产物以及转换选择性的策略。我们鼓励设计更多结合不同功能元素的复合物，以进一步优化二氧化碳还原催化剂，特别是用于形成二氧化碳以外的产物。需要更多样化的双金属催化剂，以更好地利用金属与金属之间的相互作用进行二氧化碳转化。

引用次数: 0

Synthetic transporters for oxoanions 氧阴离子合成转运体。

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-11-14 DOI: 10.1016/j.cbpa.2024.102542

Karolis Norvaisa, Aaron Torres-Huerta, Hennie Valkenier

This brief review highlights recent advances in the transport of oxoanions using synthetic carriers, focusing on both progress and ongoing challenges in the field. The difficulty of transporting these oxoanions increases with their hydration enthalpies, with less hydrated nitrate and perchlorate being relatively easy to transport. Recent progress has focused on the transport of moderately hydrated anions such as bicarbonate and carboxylates, where studies are influenced by the free diffusion of neutral species obtained by (de)protonation equilibria. Despite significant innovations in the design of synthetic carriers, the transport of the highly hydrated oxoanions sulfate and phosphate remains a major challenge. Progress on sulfate transport has stalled, while the first example of phosphate transport was reported only last year.

这篇简短的综述重点介绍了利用合成载体传输氧阴离子的最新进展，重点关注该领域的进展和当前面临的挑战。运输这些氧阴离子的难度随其水化焓的增加而增加，水化程度较低的硝酸盐和高氯酸盐相对容易运输。最近的研究进展主要集中在中度水合阴离子（如碳酸氢盐和羧酸盐）的迁移上，其研究受到了通过（去）质子化平衡获得的中性物质自由扩散的影响。尽管在合成载体的设计方面取得了重大创新，但硫酸根和磷酸根等高水合氧阴离子的传输仍然是一项重大挑战。硫酸盐迁移方面的研究进展停滞不前，而磷酸盐迁移方面的第一个实例直到去年才有报道。

引用次数: 0

Corrigendum to “Compounds for selective translational inhibition” [Curr Opin Chem Biol 69 (2022) 102158] 对 "选择性翻译抑制化合物 "的更正 [Curr Opin Chem Biol 69 (2022) 102158]

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-11-06 DOI: 10.1016/j.cbpa.2024.102543

Yuichi Shichino , Shintaro Iwasaki

引用次数: 0

Designing small-molecule and macromolecule sensors for imaging redox-active transition metal signaling 设计用于成像氧化还原活性过渡金属信号的小分子和大分子传感器

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-11-04 DOI: 10.1016/j.cbpa.2024.102541

Aidan T. Pezacki , Jiaying Gao , Christopher J. Chang

Transition metals play essential roles in biology, where these nutrients regulate protein activity as active site cofactors or via metalloallostery. In contrast, dysregulation of transition metal homeostasis can lead to unique metal-dependent signaling pathways connected to aging and disease, such as cuproptosis and ferroptosis for copper- and iron-dependent cell death or cuproplasia and ferroplasia for copper- and iron-dependent cell growth and proliferation, respectively. New methods that enable detection of bioavailable transition metal pools with both metal and oxidation state specificity can help decipher their contributions to health and disease. Here we summarize recent advances in designing sensors for imaging transition metals and their applications to uncover new metal biology.

过渡金属在生物学中发挥着至关重要的作用，这些营养物质作为活性位点辅助因子或通过金属变质作用调节蛋白质的活性。相反，过渡金属平衡失调会导致与衰老和疾病相关的独特的金属依赖性信号通路，如杯突症和铁突症分别导致铜和铁依赖性细胞死亡，或杯增生和铁增生分别导致铜和铁依赖性细胞生长和增殖。采用新方法检测具有金属和氧化态特异性的生物可利用过渡金属池，有助于破解它们对健康和疾病的影响。在此，我们总结了设计过渡金属成像传感器的最新进展及其在揭示新金属生物学方面的应用。

引用次数: 0

Microbial metabolite-receptor interactions in the gut microbiome 肠道微生物群中微生物代谢物与受体之间的相互作用。

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-10-25 DOI: 10.1016/j.cbpa.2024.102539

Pamela V. Chang

The gut microbiome impacts many physiological processes that greatly influence host health and disease. Metabolites produced by the gut microbiota have emerged as central players in regulating these biological pathways, often through the engagement of specific host receptors. Despite the importance of these microbial metabolites and receptors in human biology, the vast majority of these interactions remain uncharted due to the complex nature of the gut microbiome and the multitude of metabolites that these microbes produce. Here, we highlight recent developments in identifying such host-gut microbiota interactions, including characterization of bioactive metabolites and their mechanisms of action. Understanding these pathways will enable the development of prophylactics and therapeutics for treating many inflammatory diseases that are impacted by the gut microbiota.

肠道微生物群影响着许多生理过程，对宿主的健康和疾病有很大影响。肠道微生物群产生的代谢物已成为调节这些生物通路的核心角色，通常是通过与特定的宿主受体相互作用来实现的。尽管这些微生物代谢物和受体在人类生物学中非常重要，但由于肠道微生物群的复杂性和这些微生物产生的大量代谢物，这些相互作用中的绝大部分仍是未知的。在此，我们将重点介绍在确定这种宿主-肠道微生物群相互作用方面的最新进展，包括生物活性代谢物的特征及其作用机制。了解这些途径将有助于开发预防和治疗药物，以治疗受肠道微生物群影响的多种炎症性疾病。

引用次数: 0

Drug discovery targeting Nav1.8: Structural insights and therapeutic potential 以 Nav1.8 为靶点的药物发现：结构见解和治疗潜力

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-10-17 DOI: 10.1016/j.cbpa.2024.102538

Huan Wang , Jian Huang , Jie Zang , Xueqin Jin , Nieng Yan

Voltage-gated sodium (Na_v) channels are crucial in transmitting action potentials in neurons. The tetrodotoxin-resistant subtype Na_v1.8 is predominantly expressed in the peripheral nervous system, offering a unique opportunity to design selective inhibitors for pain relief. A number of compounds have been reported to specifically block Na_v1.8. Among these, VX-548 is already in regulatory review for the treatment of moderate-to-severe acute pain and holds the promise to be the first non-opioid pain killer over the past twenty years. Recent structural studies using cryogenic electron microscopy (cryo-EM) and structure-based predictive modeling have provided unprecedented insights into the structural pharmacology of Na_v1.8. In this review, we summarize the latest developments in Na_v1.8-selective inhibitors, focusing on the druggable sites and mechanisms that confer subtype specificity. These structural insights highlight the potential for Na_v1.8 inhibitors to deliver non-addictive pain management, thus illuminating the avenue to next-generation analgesic development.

电压门控钠（Nav）通道是神经元传递动作电位的关键。耐河豚毒素亚型 Nav1.8 主要在外周神经系统中表达，这为设计用于缓解疼痛的选择性抑制剂提供了独特的机会。据报道，许多化合物都能特异性阻断 Nav1.8。其中，VX-548 已进入监管审查阶段，用于治疗中度至重度急性疼痛，有望成为过去二十年来首个非阿片类止痛药。最近利用低温电子显微镜（cryo-EM）和基于结构的预测模型进行的结构研究为 Nav1.8 的结构药理学提供了前所未有的见解。在这篇综述中，我们总结了 Nav1.8 选择性抑制剂的最新进展，重点介绍了赋予亚型特异性的可药用位点和机制。这些结构性见解凸显了 Nav1.8 抑制剂提供非成瘾性疼痛治疗的潜力，从而为下一代镇痛药的开发指明了道路。

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引用次数: 0

Beyond chloroquine: Cationic amphiphilic drugs as endosomal escape enhancers for nucleic acid therapeutics 超越氯喹：阳离子两亲药物作为核酸治疗药物的内体逸出增强剂。

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2024-10-05 DOI: 10.1016/j.cbpa.2024.102531

Aliona Debisschop , Bram Bogaert , Cristina Muntean , Stefaan C. De Smedt , Koen Raemdonck

Nucleic acid (NA) therapeutics have the potential to treat or prevent a myriad of diseases but generally require cytosolic delivery to be functional. NA drugs are therefore often encapsulated into delivery systems that mediate effective endocytic uptake by target cells, but unfortunately often display limited endosomal escape efficiency. This review will focus on the potential of repurposing cationic amphiphilic drugs (CADs) to enhance endosomal escape. In general terms, CADs are small molecules with one or more hydrophobic groups and a polar domain containing a basic amine. CADs have been reported to accumulate in acidified intracellular compartments (e.g., endosomes and lysosomes), integrate in cellular membranes and alter endosomal trafficking pathways, ultimately resulting in improved cytosolic release of the endocytosed cargo. As many CADs are widely used drugs, their repurposing offers opportunities for combination therapies with NAs.

核酸（NA）疗法有可能治疗或预防多种疾病，但通常需要通过胞吐传递才能发挥作用。因此，核酸药物通常被封装在递送系统中，以促进靶细胞的有效内吞，但不幸的是，内吞效率往往有限。本综述将重点探讨阳离子两亲药物（CADs）的再利用潜力，以提高内泌体转运能力。一般来说，CADs 是具有一个或多个疏水基团和一个含有碱性胺的极性域的小分子。据报道，CADs 可在酸化的细胞内区室（如内体和溶酶体）中积聚，整合到细胞膜中，并改变内体转运途径，最终改善内吞货物的胞浆释放。由于许多 CADs 都是广泛使用的药物，因此它们的再利用为与 NAs 的联合疗法提供了机会。

引用次数: 0

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