Journal of the American Chemical Society最新文献_第2页

Ligand-Enabled Selective Coupling of MIDA Boronates to Dehydroalanine-Containing Peptides and Proteins

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-21 DOI: 10.1021/jacs.4c16525

Alexander A. Vinogradov, Shih-Yu Pan, Hiroaki Suga

{"title":"Ligand-Enabled Selective Coupling of MIDA Boronates to Dehydroalanine-Containing Peptides and Proteins","authors":"Alexander A. Vinogradov, Shih-Yu Pan, Hiroaki Suga","doi":"10.1021/jacs.4c16525","DOIUrl":"https://doi.org/10.1021/jacs.4c16525","url":null,"abstract":"α,β-dehydroalanine (ΔAla) is a uniquely reactive nonproteinogenic amino acid often employed for the late-stage functionalization of peptides, natural products (NPs), and proteins. The modification of ΔAla is a powerful method for the semisynthetic engineering of NPs and for post-translational protein mutagenesis. Numerous enabling ΔAla modification techniques have been developed over the years, but most state-of-the-art approaches furnish product mixtures detrimental in many applications. Here, we report a Pd(II)-mediated coupling reaction between aryl N-methylimidodiacetic acid boronates and ΔAla-containing peptides and proteins which yields ΔzPhe coupling products with high selectivity. The coupling proceeds in water under ambient conditions (37 °C, <24 h) and without the exclusion of oxygen using fully unprotected substrates. The speed and high selectivity of the reaction is enabled by the use of N,N′-ethylene-bis-Lthreonine as a Pd(II) ligand. We utilize this chemistry to selectively functionalize a variety of oligopeptides, NP-like compounds, and intact proteins. Finally, we show that the coupling reaction can be readily adapted to modify in vitro translated peptides by devising a platform for the chemoribosomal synthesis of ΔzPhe-containing structures. Altogether, our chemistry provides a powerful tool for the selective late-stage functionalization of ΔAla in peptides and proteins.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"48 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470648","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}

引用次数: 0

Synthesis and Stabilization of a Benzene Dianion with a Triplet Ground State and Baird Aromaticity

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-21 DOI: 10.1021/jacs.4c17459

Yi Wang, Rong Sun, Jiefeng Liang, Yurou Zhang, Bowen Tan, Chong Deng, Yi-Han Wang, Bing-Wu Wang, Song Gao, Wenliang Huang

引用次数: 0

Discovery of Cysteine Carboxyalkylations by Real-Time Isotopic Signature Targeted Profiling

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-21 DOI: 10.1021/jacs.4c16183

Guogeng Jia, Yicheng Liu, Tianyu Feng, Zixuan Zhang, Huan Tang, Fan Yang, Ziyao Tang, Weidi Xiao, Ying Chen, Jinjun Gao, Chu Wang

引用次数: 0

Triggered Inversion of Dual Responsive Diblock Copolypeptide Vesicles.

IF 14.4 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c17033

Casey A Morrison, Ethan P Chan, Timothy J Deming

{"title":"Triggered Inversion of Dual Responsive Diblock Copolypeptide Vesicles.","authors":"Casey A Morrison, Ethan P Chan, Timothy J Deming","doi":"10.1021/jacs.4c17033","DOIUrl":"https://doi.org/10.1021/jacs.4c17033","url":null,"abstract":"We report the synthesis of amphiphilic poly(l-methionine sulfoxide)x-b-poly(dehydroalanine)y, diblock copolypeptides, MOxADHy, and their self-assembly into submicrometer-diameter unilamellar vesicles in aqueous media. The formation of vesicles was observed over an unprecedented range of copolypeptide compositions due to the unique properties and chain conformations of ADH hydrophobic segments. These copolypeptides incorporate two distinct thiol reactive components where each segment can respond differently to a single thiol stimulus. Incubation of MO35ADH30 vesicles with glutathione under intracellular mimetic conditions resulted in vesicle disruption and release of cargo. Further, incubation of MO35ADH30 vesicles with thiolglycolic acid resulted in a reversal of amphipilicity and successful in situ inversion of the vesicle assemblies. This conversion of biomimetic polymer vesicles into stable inverted vesicles using a biologically relevant stimulus at physiological pH and temperature is unprecedented. These results provide insights toward the development of advanced functional synthetic assemblies with potential uses in biology and medicine.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456264","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}

引用次数: 0

Non-van-der-Waals Oriented Two-Dimensional UiO-66 Films by Rapid Aqueous Synthesis at Room Temperature

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c11134

Heng-Yu Chi, Shuqing Song, Kangning Zhao, Kuang-Jung Hsu, Qi Liu, Yueqing Shen, Anne Faustine Sido Belin, Arthur Allaire, Ranadip Goswami, Wendy L. Queen, Kumar Varoon Agrawal

{"title":"Non-van-der-Waals Oriented Two-Dimensional UiO-66 Films by Rapid Aqueous Synthesis at Room Temperature","authors":"Heng-Yu Chi, Shuqing Song, Kangning Zhao, Kuang-Jung Hsu, Qi Liu, Yueqing Shen, Anne Faustine Sido Belin, Arthur Allaire, Ranadip Goswami, Wendy L. Queen, Kumar Varoon Agrawal","doi":"10.1021/jacs.4c11134","DOIUrl":"https://doi.org/10.1021/jacs.4c11134","url":null,"abstract":"The synthesis of MOFs in a two-dimensional (2D) film morphology is attractive for several applications including molecular and ionic separation. However, 2D MOFs have only been reported from structures that crystallize in lamellar morphology, where layers are held together by van der Waals (vdW) interaction. By comparison, UiO-66, one of the most studied MOFs because of its exceptional chemical stability, has only been reported in three-dimensional (3D) morphology. 2D UiO-66 is challenging to obtain given the robust isotropic bonds in its cubic crystal structure. Herein, we report the first synthesis of non-vdW 2D UiO-66-NH2 by developing crystal growth conditions that promote in-plane growth over out-of-plane growth. Continuous, oriented UiO-66-NH2 film with thickness tunable in the range of 0.5 to 2 unit cells could be obtained by sustainable, scalable chemistry, which yielded attractive ion–ion selectivity. The preparation of non-vdW 2D MOF is highly attractive to advance the field of MOF films for diverse applications.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"52 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462719","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}

引用次数: 0

Temperature-Dependent Mixed Valency in the Hexagonal Perovskite Cs₃NaFe₂Cl₉.

IF 14.4 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c17019

David Liu, Alexander Milder, Jeremiah Stevens, Cierra Foster, Brendan Beck, Maxim Avdeev, Patrick M Woodward

{"title":"Temperature-Dependent Mixed Valency in the Hexagonal Perovskite Cs3NaFe2Cl9.","authors":"David Liu, Alexander Milder, Jeremiah Stevens, Cierra Foster, Brendan Beck, Maxim Avdeev, Patrick M Woodward","doi":"10.1021/jacs.4c17019","DOIUrl":"https://doi.org/10.1021/jacs.4c17019","url":null,"abstract":"The hexagonal perovskites Cs3NaFe2Cl9 and Cs3NaMnFeCl9 have been synthesized and investigated. Both compounds adopt the 6H perovskite structure with P63/mmc symmetry. This structure consists of dimers of face-sharing octahedra arranged on the vertices of a triangular network. The transition metal ions occupy sites in these octahedra, leading to Fe2Cl94- and FeMnCl94- bioctahedra, respectively. The bioctahedral clusters are sandwiched by layers of corner-sharing octahedra occupied by Na+ cations. Diffuse reflectance spectroscopy reveals optical transitions that arise from metal-to-metal charge transfer (Cs3NaMnFeCl9) and intervalence charge transfer (Cs3NaFe2Cl9) excitations. In Cs3NaFe2Cl9, magnetic susceptibility measurements reveal local ferromagnetic coupling (θCW = 16.7 K), mediated by the rapid exchange of an electron between the iron sites within each dimer. In contrast, the magnetic coupling between Fe3+ and Mn2+ in Cs3NaMnFeCl9 is antiferromagnetic (θCW = -41.4 K). At 100 K, the Mössbauer spectrum is dominated by a single type of iron that corresponds to Fe2.5+, signaling electron exchange between iron sites that is faster than the Mössbauer time scale (∼100 ns). Upon further cooling, the Fe2.5+ signal gives way to a 1:1 ratio of Fe2+ and Fe3+, as the thermally activated hopping slows down.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456262","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}

引用次数: 0

Hierarchical Reaction Logic Enables Computational Design of Complex Peptide Syntheses

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c17057

Karol Molga, Wiktor Beker, Rafał Roszak, Andrzej Czerwiński, Bartosz A. Grzybowski

{"title":"Hierarchical Reaction Logic Enables Computational Design of Complex Peptide Syntheses","authors":"Karol Molga, Wiktor Beker, Rafał Roszak, Andrzej Czerwiński, Bartosz A. Grzybowski","doi":"10.1021/jacs.4c17057","DOIUrl":"https://doi.org/10.1021/jacs.4c17057","url":null,"abstract":"The prevalent assumption in computer-assisted synthesis planning has been to rely on the wealth of reaction data and on the consideration of this vast knowledge base at every stage of route planning. Yet even if equipped with all requisite knowledge of individual reaction transforms and state-of-the-art search algorithms, the existing programs struggle when confronted with advanced targets, such as the complex peptides this work considers. By contrast, when the searches are constrained by hierarchical logic, dictating which subsets of reactions to apply at different stages of synthesis planning, these algorithms are able to plan, within minutes, complete routes to clinically relevant targets as complex as vancomycin and as large as semaglutide. Despite not being trained on any literature precedents, the routes designed by the algorithm mimic the strategies used by human experts. The hierarchical planning we describe incorporates protecting-group strategies and realistic pathway pricing and can be performed in solid-state or solution modes, in the latter case using either C-to-N or N-to-C peptide extension strategies.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"2 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462778","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}

引用次数: 0

Intracellular Photocatalytic NADH/NAD(P)H Oxidation for Cancer Drug Development

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c18328

Ashish Kumar Yadav, Rajesh Kushwaha, Arif Ali Mandal, Apurba Mandal, Samya Banerjee

{"title":"Intracellular Photocatalytic NADH/NAD(P)H Oxidation for Cancer Drug Development","authors":"Ashish Kumar Yadav, Rajesh Kushwaha, Arif Ali Mandal, Apurba Mandal, Samya Banerjee","doi":"10.1021/jacs.4c18328","DOIUrl":"https://doi.org/10.1021/jacs.4c18328","url":null,"abstract":"Photocatalytic cancer therapy (PCT) has emerged as a cutting-edge anticancer mechanism of action, harnessing light energy to mediate the catalytic oxidation of intracellular substrates. PCT is of significant current importance due to its potential to address the limitations of conventional chemotherapy, particularly drug resistance and side effects. This approach offers a noninvasive, targeted cancer treatment option by utilizing metal-based photocatalysts to induce redox and metabolic disorders within cancer cells. The photocatalysts disrupt the cancer cell metabolism by converting NADH/NAD(P)H to NAD+/NAD(P)+ via catalytic photoredox processes, altering intracellular NAD+/NADH or NAD(P)+/NAD(P)H ratios, which are crucial for cellular metabolism. Ir(III), Ru(II), Re(I), and Os(II) photocatalysts demonstrated promising PCT efficacy. Despite these developments, gaps remain in the literature for translating this new anticancer mechanism into clinical trials. This Perspective critically examines the developments in this research area and provides future directions for designing efficient photocatalysts for PCT.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"31 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462781","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}

引用次数: 0

Pyridinium Rotor Strategy toward a Robust Photothermal Agent for STING Activation and Multimodal Image-Guided Immunotherapy for Triple-Negative Breast Cancer

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c15534

Shipeng Ning, Ping Shangguan, Xinyan Zhu, Xinwen Ou, Kaiyuan Wang, Meng Suo, Hanchen Shen, Xiuxin Lu, Xianqing Wei, Tianfu Zhang, Xiaoyuan Chen, Ben Zhong Tang

{"title":"Pyridinium Rotor Strategy toward a Robust Photothermal Agent for STING Activation and Multimodal Image-Guided Immunotherapy for Triple-Negative Breast Cancer","authors":"Shipeng Ning, Ping Shangguan, Xinyan Zhu, Xinwen Ou, Kaiyuan Wang, Meng Suo, Hanchen Shen, Xiuxin Lu, Xianqing Wei, Tianfu Zhang, Xiaoyuan Chen, Ben Zhong Tang","doi":"10.1021/jacs.4c15534","DOIUrl":"https://doi.org/10.1021/jacs.4c15534","url":null,"abstract":"The immunosuppressive tumor microenvironment in triple-negative breast cancer could hinder the response to thorough immunotherapy and diminish the antitumor efficacy. Although the STING pathway emerges as a promising target to remedy defects, uncertain drug delivery might lead to off-target inflammatory reactions. Here, we manifest a novel phototheranostic agent with an aggregation-induced emission property that guided the pharmacological activation of a STING agonist for photothermal immunotherapy to create an immunologically “hot” tumor. A pyridinium rotor strategy is proposed to develop a positively charged TBTP-Bz, which is stably coincorporated with a STING agonist MSA-2 into thermal-responsive exosome-liposome hybrid nanoparticles for tumor-targeting delivery. TBTP-Bz exhibits aggregation-enhanced NIR-II emission and a photoacoustic signal, accomplishing real-time tumor tracking. Its photothermal stimulation induces immunogenic cancer cell death and promotes the precise release of MSA-2, thus boosting STING activation and STING-mediated type I interferon production. Significantly, single-dose photoimmunotherapy effectively suppresses abscopal tumor growth and provokes an immune memory effect to inhibit postsurgical recurrent and rechallenged tumors. This demonstrates promising clinical potential for poorly immunogenic breast cancer.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"16 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462775","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}

引用次数: 0

Amplifying Magnetic Field Effects on Upconversion Emission via Molecular Qubit-Driven Triplet-Triplet Annihilation.

IF 14.4 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c16922

Neo Lin, Tomoyasu Mani

{"title":"Amplifying Magnetic Field Effects on Upconversion Emission via Molecular Qubit-Driven Triplet-Triplet Annihilation.","authors":"Neo Lin, Tomoyasu Mani","doi":"10.1021/jacs.4c16922","DOIUrl":"https://doi.org/10.1021/jacs.4c16922","url":null,"abstract":"Triplet-triplet annihilation (TTA) enables photon upconversion by combining two lower-energy triplet excitons to produce a higher-energy singlet exciton. This mechanism enhances light-harvesting efficiency for solar energy conversion and enables the use of lower-energy photons in bioimaging and photoredox catalysis applications. The magnetic modulation of such high-energy excitons presents an exciting opportunity to develop molecular quantum information technologies. While the spin dynamics of triplet exciton pairs are sensitive to external magnetic fields, the magnetic field effects (MFEs) associated with these pairs are generally limited by spin statistics to at most 10% at low fields (<1 T), making them challenging to apply in technological advancements. In contrast, MFEs on spin-correlated radical pairs (SCRPs) can be significantly greater, surpassing those on triplet pairs. By using SCRPs-based molecular qubits as triplet sensitizers in the sensitized TTA scheme, we can magnetically modulate TTA and consequently, the delayed fluorescence of annihilators. In our current system, we have achieved more than 70% magnetic modulation of delayed fluorescence, effectively harnessing and even amplifying magnetic modulation within SCRPs to influence high-energy excitons. This work opens new opportunities for advancing spin-controlled chemical reactions and molecular quantum information technologies.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456253","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}

引用次数: 0