Communications Chemistry最新文献_第2页

Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosis 环境敏感型开启荧光探针可对母细胞瘤形成过程中髓过氧化物酶的活性进行活细胞成像

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-12 DOI: 10.1038/s42004-024-01338-5

Enebie Ramos Cáceres, Lotte Kemperman, Kimberly M. Bonger

{"title":"Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosis","authors":"Enebie Ramos Cáceres, Lotte Kemperman, Kimberly M. Bonger","doi":"10.1038/s42004-024-01338-5","DOIUrl":"10.1038/s42004-024-01338-5","url":null,"abstract":"Myeloperoxidase (MPO) plays an important role in the immune response of human neutrophils and has been implicated in autoimmune conditions, cardiovascular disorders, and neurodegeneration. Current methods to detect MPO activity rely on the detection of HOCl using activatable probes or require challenging experimental procedures. Therefore, these tools provide limited information about the dynamics and localization of MPO in complex molecular processes such as NETosis in real time. In this study, we report a ‘’turn-on” activity-based probe that fluoresces exclusively upon binding to MPO, exhibits minimal background fluorescence in buffered aqueous media, and is blocked by MPO inhibitors. Our probe facilitates real-time imaging of direct MPO activity in human neutrophils and HL-60-derived granulocytes during NETosis under wash-free conditions. Furthermore, it allows for the discrimination between different triggers of NETosis in human neutrophils. These findings hold promise for advancing our understanding of the role of MPO in immune responses and inflammatory conditions. Myeloperoxidase (MPO) plays an important role in the innate immune response of human neutrophils and has been implicated in various diseases, but current methods to detect MPO provide limited information about its dynamics and localization in complex molecular processes. Here, the authors develop an activity-based probe that fluoresces exclusively upon binding to MPO, enabling real-time imaging of direct intracellular MPO activity in human neutrophils and HL-60-derived granulocytes during NETosis under wash-free conditions.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-7"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01338-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liquid-liquid crystalline phase separation of spider silk proteins 蜘蛛丝蛋白质的液-液结晶相分离

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-12 DOI: 10.1038/s42004-024-01357-2

Michael Landreh, Hannah Osterholz, Gefei Chen, Stefan D. Knight, Anna Rising, Axel Leppert

{"title":"Liquid-liquid crystalline phase separation of spider silk proteins","authors":"Michael Landreh, Hannah Osterholz, Gefei Chen, Stefan D. Knight, Anna Rising, Axel Leppert","doi":"10.1038/s42004-024-01357-2","DOIUrl":"10.1038/s42004-024-01357-2","url":null,"abstract":"Liquid-liquid phase separation (LLPS) of proteins can be considered an intermediate solubility regime between disperse solutions and solid fibers. While LLPS has been described for several pathogenic amyloids, recent evidence suggests that it is similarly relevant for functional amyloids. Here, we review the evidence that links spider silk proteins (spidroins) and LLPS and its role in the spinning process. Major ampullate spidroins undergo LLPS mediated by stickers and spacers in their repeat regions. During spinning, the spidroins droplets shift from liquid to crystalline states. Shear force, altered ion composition, and pH changes cause micelle-like spidroin assemblies to form an increasingly ordered liquid-crystalline phase. Interactions between polyalanine regions in the repeat regions ultimately yield the characteristic β-crystalline structure of mature dragline silk fibers. Based on these findings, we hypothesize that liquid-liquid crystalline phase separation (LLCPS) can describe the molecular and macroscopic features of the phase transitions of major ampullate spidroins during spinning and speculate whether other silk types may use a similar mechanism to convert from liquid dope to solid fiber. Liquid-liquid phase separation (LLPS) of proteins can be considered an intermediate solubility regime between disperse solutions and solid fibers, relevant to both pathogenic and functional amyloids. Here, the authors review the evidence that links spider silk proteins (spidroins) and LLPS and its role in the spinning process.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-8"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01357-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DigFrag as a digital fragmentation method used for artificial intelligence-based drug design DigFrag 作为一种数字碎裂方法，用于基于人工智能的药物设计

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-11 DOI: 10.1038/s42004-024-01346-5

Ruoqi Yang, Hao Zhou, Fan Wang, Guangfu Yang

{"title":"DigFrag as a digital fragmentation method used for artificial intelligence-based drug design","authors":"Ruoqi Yang, Hao Zhou, Fan Wang, Guangfu Yang","doi":"10.1038/s42004-024-01346-5","DOIUrl":"10.1038/s42004-024-01346-5","url":null,"abstract":"Fragment-Based Drug Design (FBDD) plays a pivotal role in the field of drug discovery and development. The construction of high-quality fragment libraries is a critical step in FBDD. Conventional fragmentation approaches often rely on rigid rules and chemical intuition, limiting their adaptability to diverse molecular structures. The rapid development of Artificial Intelligence (AI) technology offers a transformative opportunity to rethink traditional methods. Here, we present DigFrag, a digital fragmentation method that highlights important substructures by focusing locally within the molecular graph. In addition, we feed the fragments segmented by machine intelligence and human expertise into the deep generative model to compare the preference for data from different sources. Experimental results show that the structural diversity of fragments segmented by DigFrag is higher, and more desirable compounds are generated based on these fragments. These results also demonstrate that data generated based on AI methods may be more suitable for AI models. Moreover, a user-friendly platform called MolFrag ( https://dpai.ccnu.edu.cn/MolFrag/ ) is developed based on various fragmentation techniques to support molecular segmentation. Fragment-based drug design plays a pivotal role in the field of drug discovery and development, however, the construction of high-quality fragment libraries is a critical but challenging step. Here, the authors develop DigFrag, a digital fragmentation method based on the graph attention mechanism, showing higher structural diversity of the fragments and higher applicability to artificial intelligence-based drug design.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-9"},"PeriodicalIF":5.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01346-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pivotal role of 99Tc NMR spectroscopy in solid-state and molecular chemistry 99Tc NMR 光谱在固态和分子化学中的关键作用

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-11 DOI: 10.1038/s42004-024-01349-2

Vitaly V. Kuznetsov, Frederic Poineau, Konstantin E. German, Elena A. Filatova

引用次数: 0

On the interfacial phenomena at the Li7La3Zr2O12 (LLZO)/Li interface 关于 Li7La3Zr2O12 (LLZO)/Li 界面的界面现象

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-09 DOI: 10.1038/s42004-024-01350-9

Kostiantyn V. Kravchyk, Huanyu Zhang, Maksym V. Kovalenko

引用次数: 0

Bacteriophage-related epigenetic natural and non-natural pyrimidine nucleotides and their influence on transcription with T7 RNA polymerase 噬菌体相关表观遗传天然和非天然嘧啶核苷酸及其对 T7 RNA 聚合酶转录的影响

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-09 DOI: 10.1038/s42004-024-01354-5

Filip Gracias, Radek Pohl, Veronika Sýkorová, Michal Hocek

{"title":"Bacteriophage-related epigenetic natural and non-natural pyrimidine nucleotides and their influence on transcription with T7 RNA polymerase","authors":"Filip Gracias, Radek Pohl, Veronika Sýkorová, Michal Hocek","doi":"10.1038/s42004-024-01354-5","DOIUrl":"10.1038/s42004-024-01354-5","url":null,"abstract":"DNA modifications on pyrimidine nucleobases play diverse roles in biology such as protection of bacteriophage DNA from enzymatic cleavage, however, their role in the regulation of transcription is underexplored. We have designed and synthesized a series of uracil 2ʹ-deoxyribonucleosides and 5ʹ-O-triphosphates (dNTPs) bearing diverse modifications at position 5 of nucleobase, including natural nucleotides occurring in bacteriophages, α-putrescinylthymine, α-glutaminylthymine, 5-dihydroxypentyluracil, and methylated or non-methylated 5-aminomethyluracil, and non-natural 5-sulfanylmethyl- and 5-cyanomethyluracil. The dNTPs bearing basic substituents were moderate to poor substrates for DNA polymerases, but still useful in primer extension synthesis of modified DNA. Together with previously reported epigenetic pyrimidine nucleotides, they were used for the synthesis of diverse DNA templates containing a T7 promoter modified in the sense, antisense or in both strands. A systematic study of the in vitro transcription with T7 RNA polymerase showed a moderate positive effect of most of the uracil modifications in the non-template strand and some either positive or negative influence of modifications in the template strand. The most interesting modification was the non-natural 5-cyanomethyluracil which showed significant positive effect in transcription. DNA modifications on pyrimidine nucleobases play diverse roles in biology such as protection of bacteriophage DNA from enzymatic cleavage, however, their role in the regulation of transcription is underexplored. Here, the authors design and synthesize a series of 5-substituted pyrimidine 2ʹ-deoxyribonucleoside triphosphates and employ them for the synthesis of diverse DNA templates, showing their regulation on in vitro transcription with T7 RNA polymerase.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":5.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01354-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rotaxanes with a photoresponsive macrocycle modulate the lipid bilayers of large and giant unilamellar vesicles 具有光致伸缩性大环的轮烷可调节大型和巨型单拉美米尔囊泡的脂质双分子层

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-08 DOI: 10.1038/s42004-024-01343-8

Udyogi N. K. Conthagamage, Rajitha Rajeshwar T, Stijn van der Ham, Nasim Akhtar, Macallister L. Davis, Senuri G. Jayawardana, Lilia Lopez, Hanumantha Rao Vutukuri, Jeremy C. Smith, Micholas Dean Smith, Víctor García-López

{"title":"Rotaxanes with a photoresponsive macrocycle modulate the lipid bilayers of large and giant unilamellar vesicles","authors":"Udyogi N. K. Conthagamage, Rajitha Rajeshwar T, Stijn van der Ham, Nasim Akhtar, Macallister L. Davis, Senuri G. Jayawardana, Lilia Lopez, Hanumantha Rao Vutukuri, Jeremy C. Smith, Micholas Dean Smith, Víctor García-López","doi":"10.1038/s42004-024-01343-8","DOIUrl":"10.1038/s42004-024-01343-8","url":null,"abstract":"Rotaxanes equipped with actuators hold great potential for developing highly functional molecular machines. Such systems could significantly enhance our ability to study and manipulate biological and artificial membranes. Here, we introduce a rotaxane with a ring featuring two azobenzene photoswitches, which retain their photoreversibility and can be stochastically shuttled along the axle in solution. Studies in model bilayers, supported by molecular dynamics simulations, show how azobenzene photoswitching alters the interaction of rotaxanes with surrounding lipids, leading to changes in lipid packing. Such changes in the lipid bilayer were leveraged to induce the light-triggered release of sulforhodamine B from large unilamellar vesicles. Additionally, light activation of the rotaxanes is shown to induce reversible contraction and expansion of giant unilamellar vesicles. The results provide novel insights into the interactions and operation of rotaxanes in lipid bilayers and their impact on membrane properties. This will aid in developing systems for precise membrane manipulation for applications in biomedicine and bioengineering. Rotaxanes equipped with actuators hold great potential for developing highly functional molecular machines, and could enhance our ability to study and manipulate biological and artificial membranes. Here, the authors introduce a rotaxane with a ring that features two azobenzene photoswitches, and demonstrate that photoswitching can be used to reversibly modulate lipid bilayer structure. This capability was exploited for the light-triggered release of sulforhodamine B from large unilamellar vesicles.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":5.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01343-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-07 DOI: 10.1038/s42004-024-01334-9

Maximilián Lamanec, Svatopluk Civiš, Pavel Hobza

{"title":"On the similar spectral manifestations of protonic and hydridic hydrogen bonds despite their different origin","authors":"Maximilián Lamanec, Svatopluk Civiš, Pavel Hobza","doi":"10.1038/s42004-024-01334-9","DOIUrl":"10.1038/s42004-024-01334-9","url":null,"abstract":"Previously studied complexes with protonic and hydridic hydrogen bonds exhibit significant similarities. The present study provides a detailed investigation of the structure, stabilization, electronic properties, and spectral characteristics of protonic and hydridic hydrogen bonds using low-temperature infrared (IR) spectroscopy and computational methods. Complexes of pentafluorobenzene with ammonia (C₆F₅H⋯NH₃) and triethylgermane with trifluoroiodomethane (Et₃GeH⋯ICF₃) were analyzed using both experimental and computational tools. Additionally, 30 complexes with protonic hydrogen bonds and 30 complexes with hydridic hydrogen bonds were studied computationally. Our findings reveal that, despite the opposite atomic charges on the hydrogens in these hydrogen bonds, and consequently the opposite directions of electron transfer in protonic and hydridic hydrogen bonds, their spectral manifestations - specifically, the red shifts in the X–H stretching frequency and the increase in intensity - are remarkably similar. The study also discusses the limitations of the current IUPAC definition of hydrogen bonding in covering both types of H-bonds and suggests a way to overcome these limitations. Understanding hydrogen-bonding is essential for many fields of natural science. Here, the authors investigate protonic and hydridic hydrogen bonds using low-temperature infrared spectroscopy and computational methods, finding that despite opposite atomic charges on the hydrogens in these hydrogen bonds their spectral manifestations are remarkably similar.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-7"},"PeriodicalIF":5.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01334-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Origin of the intermolecular forces that produce donor–acceptor stacks in π-conjugated charge-transfer complexes π共轭电荷转移复合物中产生供体-受体堆叠的分子间作用力的起源。

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-06 DOI: 10.1038/s42004-024-01329-6

Seiji Tsuzuki, Ryota Ono, Satoru Inoue, Satoshi Matsuoka, Tatsuo Hasegawa

{"title":"Origin of the intermolecular forces that produce donor–acceptor stacks in π-conjugated charge-transfer complexes","authors":"Seiji Tsuzuki, Ryota Ono, Satoru Inoue, Satoshi Matsuoka, Tatsuo Hasegawa","doi":"10.1038/s42004-024-01329-6","DOIUrl":"10.1038/s42004-024-01329-6","url":null,"abstract":"The attraction between π-conjugated planar electron donor and acceptor molecules that form many stable charge-transfer (CT) complexes has been explained by quantum chemical CT interactions, although the fundamental origin remains unclear. Here, we demonstrate the mechanism of CT complex formation by potential energy map analysis for TTF–CA and BTBT–TCNQ, using energy decomposition of intermolecular interaction by symmetry-adapted perturbation theory (SAPT) combined with coupled cluster calculation. We find that the source of attraction between donor and acceptor molecules is ascribed primarily to the dispersion force and also to the electrostatic force. In contrast, the contribution of CT interactions to the attractive forces is minimal. We demonstrate that the highly directional feature of the exchange repulsion force, coupled with the attractive dispersion and electrostatic forces, is crucial in determining the intermolecular arrangements of actual CT crystals. These findings are key for understanding the unique structural and electronic properties of π-conjugated CT complexes. The attraction between π-conjugated planar electron donor and acceptor molecules within charge–transfer (CT) complexes has been explained by quantum chemical CT interactions, but its fundamental origins remain unclear. Here, the authors combine symmetry-adapted perturbation theory with coupled cluster calculations to probe the mechanism of CT complex formation in crystals, finding that dispersion and electrostatic forces are dominant, with significant directional exchange repulsion.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":5.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthetic studies on the tetrasubstituted D-ring of cystobactamids lead to potent terephthalic acid antibiotics 通过对四取代 D 环的胱杆菌酰胺的合成研究，产生了强效对苯二甲酸抗生素。

IF 5.9 2区化学

Communications Chemistry Pub Date : 2024-11-05 DOI: 10.1038/s42004-024-01337-6

Moritz Stappert, Daniel Kohnhäuser, Tim Seedorf, Janetta Coetzee, Katharina Rox, Hazel L. S. Fuchs, Katarina Cirnski, Christian Leitner, Jennifer Herrmann, Andreas Kirschning, Rolf Müller, Mark Brönstrup

{"title":"Synthetic studies on the tetrasubstituted D-ring of cystobactamids lead to potent terephthalic acid antibiotics","authors":"Moritz Stappert, Daniel Kohnhäuser, Tim Seedorf, Janetta Coetzee, Katharina Rox, Hazel L. S. Fuchs, Katarina Cirnski, Christian Leitner, Jennifer Herrmann, Andreas Kirschning, Rolf Müller, Mark Brönstrup","doi":"10.1038/s42004-024-01337-6","DOIUrl":"10.1038/s42004-024-01337-6","url":null,"abstract":"Novel scaffolds for broad-spectrum antibiotics are rare and in strong demand because of the increase in antimicrobial resistance. The cystobactamids, discovered from myxobacterial sources, have a unique hexapeptidic scaffold with five arylamides and possess potent, resistance-breaking properties. This study investigates the role of the central D-ring pharmacophore in cystobactamids, a para-aminobenzoic acid (PABA) moiety that is additionally substituted by hydroxy and isopropoxy functions. We varied the two oxygenated substituents and replaced both amide connectors with bioisosteres. Synthetic routes were developed that included metal-mediated aromatic functionalization or heterocycle formations, leading to 19 novel analogues. The antibiotic efficacy of all analogues was determined against bacteria from the ESKAPE pathogen panel. While the replacement and the repositioning of hydroxy and isopropoxy substituents was not advantageous, exchanging PABA by terephthalic acid amides led to the highly potent analogue 42 with broad-spectrum activity, insensitivity towards AlbD-mediated degradation and promising pharmacokinetic properties in mice. The study highlights the steep structure-activity relationships in the tetrasubstituted D-ring and a surprisingly favorable reversion of the amide connecting C and D. Novel scaffolds for broad-spectrum antibiotics are rare and in strong demand because of the increase in antimicrobial resistance. Here, the authors assess the role of the central D ring pharmacophore in cystobactamids, and develop a potent broad-spectrum antibiotic by exchanging a para-aminobenzoic acid with a terephthalic acid amide.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-15"},"PeriodicalIF":5.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0