Angewandte Chemie (International ed. in English)最新文献

Redox Reactions with Calcium-Metal Nanoparticles. 金属钙纳米颗粒的氧化还原反应。

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-10-25 DOI: 10.1002/anie.202515995

Christian Ritschel, Anja Appenzeller, Radian Popescu, Carsten Donsbach, Ralf Köppe, Jonas O Wenzel, Frank Breher, Yolita M Eggeler, Wim Klopper, Claus Feldmann

{"title":"Redox Reactions with Calcium-Metal Nanoparticles.","authors":"Christian Ritschel, Anja Appenzeller, Radian Popescu, Carsten Donsbach, Ralf Köppe, Jonas O Wenzel, Frank Breher, Yolita M Eggeler, Wim Klopper, Claus Feldmann","doi":"10.1002/anie.202515995","DOIUrl":"https://doi.org/10.1002/anie.202515995","url":null,"abstract":"Calcium is generally a highly reactive alkaline-earth metal, but as bulk metal, it exhibits only low reactivity at ambient conditions due to small surface area, low solubility, and/or passivation. The reactivity can be significantly enhanced when using small-sized calcium nanoparticles. In this regard, we describe the first synthesis of Ca(0) nanoparticles, 5.4 ± 1.2 nm in size, by TMEDA-supported reduction of CaI2 with lithium naphthalenide in toluene (TMEDA: N,N,N',N'-tetramethylethylenediamine). We also show Ca(0) nanoparticles to be substantially different from so-called \"Rieke calcium\". The high reactivity can be used for redox reactions, for instance, with [Cp2MoCl2] and the sterically demanding β-diketiminate ligand HDippNacNac (Dipp: 2,6-iPr2C6H3) or with [(Ph3P)AuCl] as a derivative of a ligand-stabilized noble metal. The Ca(0)-nanoparticle-driven reactions result in the novel compounds [{(DippNacNac)(thf)Ca}2(naph)] (1) with a rare naphthalenide dianion, [{(DippNacNac)(thf)CaMo(Cp)H}2(fulvalene)] (2) with unusual MoH → Ca dative bonding, and [Au9(PPh3)8](naph)(tmeda)0.5 (3) with a non-charged body-centered cubic Au9 cluster core of zerovalent gold. Ca(0) nanoparticles and the compounds 1-3 are characterized by electron microscopy, X-ray diffraction (single crystals, powders), spectroscopy (IR, UV-Vis, NMR, EPR), and computation. Exemplarily, the formation of 1-3 points to the potential of nanosized alkaline-earth metals for chemical syntheses and the different reactivity of nanosized and bulk metals.","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202515995"},"PeriodicalIF":16.9,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145369369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting Aurora Kinases as Essential Cell-Cycle Regulators to Deliver Multi-Stage Antimalarials Against Plasmodium Falciparum. 靶向极光激酶作为关键细胞周期调节因子提供多阶段抗恶性疟原虫药物。

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-10-23 DOI: 10.1002/anie.202518493

Henrico Langeveld, Keletso Maepa, Marché Maree, Jessica L Thibaud, Nicolaas Salomane, Rosie Bridgwater, Mufuliat T Famodimu, Luiz C Godoy, Charisse Flerida A Pasaje, Nonlawat Boonyalai, Mariana Laureano de Souza, Justin Fong, Tayla Rabie, Mariëtte van der Watt, Rensu P Theart, Sonja Ghidelli-Disse, Jacquin C Niles, Marcus C S Lee, Elizabeth A Winzeler, Michael J Delves, Kelly Chibale, Kathryn J Wicht, Lauren B Coulson, Lyn-Marié Birkholtz

{"title":"Targeting Aurora Kinases as Essential Cell-Cycle Regulators to Deliver Multi-Stage Antimalarials Against Plasmodium Falciparum.","authors":"Henrico Langeveld, Keletso Maepa, Marché Maree, Jessica L Thibaud, Nicolaas Salomane, Rosie Bridgwater, Mufuliat T Famodimu, Luiz C Godoy, Charisse Flerida A Pasaje, Nonlawat Boonyalai, Mariana Laureano de Souza, Justin Fong, Tayla Rabie, Mariëtte van der Watt, Rensu P Theart, Sonja Ghidelli-Disse, Jacquin C Niles, Marcus C S Lee, Elizabeth A Winzeler, Michael J Delves, Kelly Chibale, Kathryn J Wicht, Lauren B Coulson, Lyn-Marié Birkholtz","doi":"10.1002/anie.202518493","DOIUrl":"https://doi.org/10.1002/anie.202518493","url":null,"abstract":"Kinases play critical roles in the development and adaptation of Plasmodium falciparum and present novel opportunities for chemotherapeutic intervention. Mitotic kinases that regulate the proliferation of the parasites by controlling nuclear division, segregation, and cytokinesis. We evaluated the potential of human Aurora kinase (Aur) inhibitors to prevent P. falciparum development by targeting members of the Aurora-related kinase (Ark) family in this parasite. Several human AurB inhibitors exhibited multistage potency (< 250 nM) against all proliferative stages of parasite development, including asexual blood stages, liver schizonts, and male gametes. The most potent compounds, hesperadin, TAE684, and AT83, exhibited > 1000x selectivity towards the parasite. Importantly, we identified PfArk1 as the principal vulnerable Ark family member, with specific inhibition of PfArk1 as the primary target for hesperadin. Hesperadin's whole-cell and protein activity validates it as a unique PfArk1 tool compound. Inhibition of PfArk1 results in the parasite's inability to complete mitotic processes, presenting with unsegregated, multi-lobed nuclei caused by aberrant microtubule organization. This suggests PfArk1 is the main Aur mitotic kinase in proliferative stages of Plasmodium, characterized by bifunctional AurA and B activity. This paves the way for drug-discovery campaigns based on hesperadin targeting PfArk1.","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202518493"},"PeriodicalIF":16.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Photoswitchable HaloTag for Spatiotemporal Control of Fluorescence in Living Cells. 一种用于活细胞荧光时空控制的光开关卤化标签。

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-10-23 DOI: 10.1002/anie.202424955

Franziska Walterspiel, Begoña Ugarte-Uribe, Jonas Weidenhausen, Merrin Vincent, Kaarjel K Narayanasamy, Anna Dimitriadi, Arif Ul Maula Khan, Martin Fritsch, Christoph W Müller, Timo Zimmermann, Claire Deo

{"title":"A Photoswitchable HaloTag for Spatiotemporal Control of Fluorescence in Living Cells.","authors":"Franziska Walterspiel, Begoña Ugarte-Uribe, Jonas Weidenhausen, Merrin Vincent, Kaarjel K Narayanasamy, Anna Dimitriadi, Arif Ul Maula Khan, Martin Fritsch, Christoph W Müller, Timo Zimmermann, Claire Deo","doi":"10.1002/anie.202424955","DOIUrl":"https://doi.org/10.1002/anie.202424955","url":null,"abstract":"Photosensitive fluorophores, whose emission can be controlled using light, are essential for advanced biological imaging, enabling precise spatiotemporal tracking of molecular features and facilitating super-resolution microscopy techniques. Although irreversibly photoactivatable fluorophores are well established, reversible reporters that can be reactivated multiple times remain scarce, and only a few have been applied in living cells using generalizable protein labeling methods. To address these limitations, we introduce chemigenetic photoswitchable fluorophores, leveraging the self-labeling HaloTag protein with fluorogenic rhodamine dye ligands. By incorporating a light-responsive protein domain into HaloTag, we engineer a tunable, photoswitchable HaloTag (psHaloTag), which can reversibly modulate the fluorescence of a bound dye-ligand via a light-induced conformational change. Our best performing psHaloTag variants show excellent performance in living cells, with large, reversible, deep-red fluorescence turn-on upon 450 nm illumination across various biomolecular targets and SMLM compatibility. Together, this work establishes the chemigenetic approach as a versatile platform for the design of photoswitchable reporters, tunable through both genetic and synthetic modifications, with promising applications for dynamic imaging.","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202424955"},"PeriodicalIF":16.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Concomitant Near-Infrared Photothermy and Photoluminescence of Rod-Shaped Au₅₂(PET)₃₂ and Au₆₆(PET)₃₈ Synthesized Concurrently. 对“同时合成的棒状Au52(PET)32和Au66(PET)38的近红外光热和光致发光”的修正。

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-10-21 DOI: 10.1002/anie.202522181

引用次数: 0

[3]CycloBODIPY: A Highly Strained Cyclic BODIPY Trimer with Effective Macrocyclic Conjugation. [3]CycloBODIPY：具有有效大环共轭的高应变环BODIPY三聚体。

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-10-21 DOI: 10.1002/anie.202519612

Masaki Sugino, Yoshitaka Tsuchido, Rento Maeda, Ichiro Hisaki, Hideaki Takano, Hiroshi Shinokubo

引用次数: 0

De Novo Design of High-Affinity Miniprotein Binders Targeting Francisella Tularensis Virulence Factor. 针对土拉菌毒力因子的高亲和力微蛋白结合物的重新设计。

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-10-21 DOI: 10.1002/anie.202516058

Gizem Gokce-Alpkilic, Buwei Huang, Andi Liu, Lieselotte S M Kreuk, Yaxi Wang, Victor Adebomi, Yensi Flores Bueso, Asim K Bera, Alex Kang, Stacey R Gerben, Stephen Rettie, Dionne K Vafeados, Nicole Roullier, Inna Goreshnik, Xinting Li, David Baker, Joshua J Woodward, Joseph D Mougous, Gaurav Bhardwaj

{"title":"De Novo Design of High-Affinity Miniprotein Binders Targeting Francisella Tularensis Virulence Factor.","authors":"Gizem Gokce-Alpkilic, Buwei Huang, Andi Liu, Lieselotte S M Kreuk, Yaxi Wang, Victor Adebomi, Yensi Flores Bueso, Asim K Bera, Alex Kang, Stacey R Gerben, Stephen Rettie, Dionne K Vafeados, Nicole Roullier, Inna Goreshnik, Xinting Li, David Baker, Joshua J Woodward, Joseph D Mougous, Gaurav Bhardwaj","doi":"10.1002/anie.202516058","DOIUrl":"https://doi.org/10.1002/anie.202516058","url":null,"abstract":"Francisella tularensis poses considerable public health risk due to its high infectivity and potential for bioterrorism. Francisella-like lipoprotein (Flpp3), a key virulence factor unique to Francisella, plays critical roles in infection and immune evasion, making it a promising target for therapeutic development. However, the lack of well-defined binding pockets and structural information on native interactions has hindered structure-guided ligand discovery against Flpp3. Here, we used a combination of physics-based and deep-learning methods to design high-affinity miniprotein binders targeting two distinct sites on Flpp3. We identified four binders for site I with binding affinities ranging between 24-110 nM. For the second site, an initial binder showed a dissociation constant (KD) of 81 nM, and subsequent site saturation mutagenesis yielded variants with sub-nanomolar affinities. Circular dichroism confirmed the topology of designed miniproteins. The X-ray crystal structure of Flpp3 in complex with a site I binder is nearly identical to the design model (Cα root-mean-square deviation (RMSD): 0.9 Å). These designed miniproteins provide research tools to explore the roles of Flpp3 in tularemia and should enable the development of new therapeutic candidates.","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202516058"},"PeriodicalIF":16.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Photochemical Di-π-Methane Rearrangement Reactions. 光化学二π-甲烷重排反应。

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-10-20 DOI: 10.1002/anie.202519769

Qi-Xin Dong, Yi-Hong Ke, Ying Zhang, Huan-Ming Huang

引用次数: 0

A Crystalline Bismuth(II) Radical Anion: Synthesis, Characterization, and Reactivity. 晶体铋（II）自由基阴离子：合成、表征和反应性。

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-10-12 DOI: 10.1002/anie.202515545

Sotirios Pavlidis, Christian Teutloff, Ana Guilherme Buzanich, Konstantin B Krause, Franziska Emmerling, Robert Bittl, Josh Abbenseth

引用次数: 0

Targeted Detection of Phospholipid Aldehydes in Living Cells by Oxime Ligation. 肟结扎法靶向检测活细胞中磷脂醛。

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-10-01 DOI: 10.1002/anie.202512578

Jacob A Vance, Wei-An Chen, Palina Nepachalovich, Caroline Knittel, Maria Fedorova, Neal K Devaraj

{"title":"Targeted Detection of Phospholipid Aldehydes in Living Cells by Oxime Ligation.","authors":"Jacob A Vance, Wei-An Chen, Palina Nepachalovich, Caroline Knittel, Maria Fedorova, Neal K Devaraj","doi":"10.1002/anie.202512578","DOIUrl":"https://doi.org/10.1002/anie.202512578","url":null,"abstract":"Oxidatively damaged lipids play critical roles in numerous human pathologies, yet methods to directly identify these species within living cells remain limited due to their transient and low-abundance nature. Among lipid oxidation products, aldehyde-containing lipids are significant due to their heightened reactivity and strong links to disease pathology. Here, we introduce OxiLox (oxime ligation to oxidized lipids), a method that leverages fluorescent hydroxylamine-based probes to enable direct, chemoselective tagging of aldehyde-containing lipids within living cells via rapid oxime ligation. Using confocal microscopy, we observe the subcellular localization of these oxidized lipids, highlighting prominent accumulation within perinuclear membranes, particularly under oxidative stress conditions induced by the ferroptosis activator RSL3. Coupled with high-resolution mass spectrometry, our method identifies aldehyde lipid species, notably revealing the abundance of oxidized plasmenyl phosphatidylethanolamines in ferroptotic cells. We demonstrate that cellular labeling by hydroxylamine probes can be modulated by altering the expression of antioxidant enzymes such as aldose reductase (AKR1B1), underscoring the relationship between enzymatic antioxidant defenses and lipid aldehyde metabolism. Our work establishes OxiLox as a robust approach for direct, sensitive, and chemically precise detection of lipid aldehydes in live cells, offering new insights into the role of lipid oxidation in health and disease.","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202512578"},"PeriodicalIF":16.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Youwei Ma.

IF 16.9

Angewandte Chemie (International ed. in English) Pub Date : 2025-09-30 DOI: 10.1002/anie.202520832

Youwei Ma

引用次数: 0