Journal of the American Chemical Society最新文献_第7页

Adding a Twist to Lateral Flow Immunoassays: A Direct Replacement of Antibodies with Helical Affibodies, from Selection to Application

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 DOI: 10.1021/jacs.4c17452

Christy J. Sadler, Adam Creamer, Kim Anh Giang, Kevion K. Darmawan, André Shamsabadi, Daniel A. Richards, Johan Nilvebrant, Jonathan P. Wojciechowski, Patrick Charchar, Ross Burdis, Francesca Smith, Irene Yarovsky, Per-Åke Nygren, Molly M. Stevens

{"title":"Adding a Twist to Lateral Flow Immunoassays: A Direct Replacement of Antibodies with Helical Affibodies, from Selection to Application","authors":"Christy J. Sadler, Adam Creamer, Kim Anh Giang, Kevion K. Darmawan, André Shamsabadi, Daniel A. Richards, Johan Nilvebrant, Jonathan P. Wojciechowski, Patrick Charchar, Ross Burdis, Francesca Smith, Irene Yarovsky, Per-Åke Nygren, Molly M. Stevens","doi":"10.1021/jacs.4c17452","DOIUrl":"https://doi.org/10.1021/jacs.4c17452","url":null,"abstract":"Immunoreagents, most commonly antibodies, are integral components of lateral flow immunoassays. However, the use of antibodies comes with limitations, particularly relating to their reproducible production, and poor thermal and chemical stability. Here, we employ phage display to develop affibodies, a class of nonimmunoglobulin affinity proteins based on a small three-helix bundle scaffold, against SARS-CoV-2 Spike protein. Subsequently, we demonstrate the utility and viability of affibodies to directly replace antibodies in lateral flow immunoassays. In addition, we highlight several physiochemical advantages of affibodies, including their ability to withstand exposure to high temperature and humidity while maintaining superior performance compared to their antibody counterparts. Furthermore, we investigate the adsorption mechanism of affibodies to the surface of gold nanoparticle probes via a His6-tag, introduced to also facilitate recombinant purification. Through molecular dynamics simulations, we elucidate the structural and physical characteristics of affibody dimers which result in high-performing detection probes when immobilized on nanoparticle surfaces. This work demonstrates that affibodies can be used as direct replacements to antibodies in immunoassays and should be further considered as alternatives owing to their improved physiochemical properties and modular design.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"71 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703083","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

De Novo Design of Proteins for Autocatalytic Isopeptide Bond Formation

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 DOI: 10.1021/jacs.5c03319

Suppachai Srisantitham, Alyssa L. Walker, Ulrich Markel, F. Akif Tezcan

{"title":"De Novo Design of Proteins for Autocatalytic Isopeptide Bond Formation","authors":"Suppachai Srisantitham, Alyssa L. Walker, Ulrich Markel, F. Akif Tezcan","doi":"10.1021/jacs.5c03319","DOIUrl":"https://doi.org/10.1021/jacs.5c03319","url":null,"abstract":"Isopeptide bonds (IPBs)─formed between the amine group of a Lys residue and the carboxamide/carboxy group of Asn/Gln or Asp/Glu─play essential roles in many biological processes, ranging from cellular signaling and regulation to blood clotting and bacterial pathogenesis. The formation of IPBs is not a spontaneous process and requires enzymatic machinery that provides a specialized active site environment to enable this challenging catalytic reaction. Here we report the de novo design and characterization of two proteins (dnIPB-1 and dnIPB-2) capable of autocatalytic IPB formation. While these designed proteins preserve the key active-site residues of their structural template (the bacterial pilin protein RrgA), they possess less than 31% sequence identity to RrgA. Extensive structural and Ala-scanning analyses indicate that IPB formation requires a solvent-protected core motif composed of several critical residues, yet there is also a large tolerance to different protein topologies and overall protein sizes in terms of accommodating an IPB-forming motif. Notably, the structural insights gained from the study of dnIPB-1 and dnIPB-2 also guided the redesign of an initially failed construct (dnIPB-3) and enabled it to form an IPB, highlighting the value of de novo design in examining sequence–structure–function relationships not explored in natural evolution. Our study highlights the versatility of IPBs as designable elements which can be used to construct functional proteins or protein-based materials with enhanced chemical, thermal, and mechanical stabilities.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"17 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713517","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

Record-High-Molecular-Weight Polyesters from Ring-Opening Copolymerization of Epoxides and Cyclic Anhydrides Catalyzed by Hydrogen-Bond-Functionalized Imidazoles

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 DOI: 10.1021/jacs.5c00426

Zhenbiao Xie, Zhenjie Yang, Chenyang Hu, Fu-Quan Bai, Nuonan Li, Zhiwei Wang, Sitian Ku, Xuan Pang, Xuesi Chen, Xianhong Wang

{"title":"Record-High-Molecular-Weight Polyesters from Ring-Opening Copolymerization of Epoxides and Cyclic Anhydrides Catalyzed by Hydrogen-Bond-Functionalized Imidazoles","authors":"Zhenbiao Xie, Zhenjie Yang, Chenyang Hu, Fu-Quan Bai, Nuonan Li, Zhiwei Wang, Sitian Ku, Xuan Pang, Xuesi Chen, Xianhong Wang","doi":"10.1021/jacs.5c00426","DOIUrl":"https://doi.org/10.1021/jacs.5c00426","url":null,"abstract":"Polyesters, with potential for degradability and sustainability, are some of the most versatile polymer materials. However, the limitation of molecular weight (MW) presents a barrier to their applications. The synthesis of polyesters with high MW by the ring-opening copolymerization (ROCOP) of epoxides and cyclic anhydrides is promising but rare and challenging. Herein, we report a series of air-stable, hydrogen-bond-functionalized imidazole catalysts for the copolymerization. These catalysts can produce polyesters (4 examples) using cyclohexane oxide (CHO), propylene oxide (PO), phenyl glycidyl ether (PGE), 4-vinyl-1-cyclohexene 1,2-epoxide (VCHO), and phthalic anhydride (PA) with record-high MW: Mn = 171.2 kDa for poly(CHO-alt-PA), Mn = 518.5 kDa for poly(PO-alt-PA), Mn = 100.5 kDa for poly(PGE-alt-PA), and Mn = 236.4 kDa for poly(VCHO-alt-PA). Furthermore, it can achieve an unprecedented efficiency of 15.6 kg of polyester/g of catalyst at a molar ratio of catalyst/PA/PO = 1:40000:60000. The record-high MW achieved can be attributed to the unique anionic-cationic coexisting ROCOP mechanism, which can reduce transesterification, chain transfer, and annulation side reactions. All high Mn polyesters showed excellent thermal stability, high tensile strength, and a Young’s modulus comparable to some commodity thermoplastics like polystyrene and polylactic acid.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"29 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713725","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

Chiral All-Inorganic Perovskite Subnanowires

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 DOI: 10.1021/jacs.5c04134

Gaoyu Chen, Kunhong Zhou, Qingda Liu, Junli Liu, Xiangxing Xu, Wenxiong Shi, Jinzhou Jiang, Xinwen Zhang, Lizhu Dong, Linghai Xie, Xiaoyu Zhang, Niuniu Zhang, Dongdong Xu, Jianchun Bao, Xun Wang

{"title":"Chiral All-Inorganic Perovskite Subnanowires","authors":"Gaoyu Chen, Kunhong Zhou, Qingda Liu, Junli Liu, Xiangxing Xu, Wenxiong Shi, Jinzhou Jiang, Xinwen Zhang, Lizhu Dong, Linghai Xie, Xiaoyu Zhang, Niuniu Zhang, Dongdong Xu, Jianchun Bao, Xun Wang","doi":"10.1021/jacs.5c04134","DOIUrl":"https://doi.org/10.1021/jacs.5c04134","url":null,"abstract":"The phenomenon of chiral symmetry breaking during the crystallization of achiral molecules or ions, which leads to the formation of controllable enantiomerically pure crystals, has garnered significant interest but remains a challenge to fully overcome. This presents a particularly formidable obstacle in the creation of three-dimensional (3D) structured chiral all-inorganic perovskites, further complicated by their achiral crystalline space groups. In this report, we successfully synthesized right- or left-handed (P/M) chiral 3D P/M-CsPbX3 (X = Cl, Cl–Br, Br, Br–I) perovskite subnanowires (SNWs), in which Pb(II) can be partially substituted by hetero ions, such as Cu(II), Sn(II), and Mn(II). The selective control of the SNW handedness was achieved through the strategic incorporation of trace chiral amine enantiomers. The chiroptical activity arises from the helical structure of the SNWs. The mechanisms underlying the formation of this chiral structure were systematically investigated and interpreted by using a thermodynamic model. We utilized the chiral P/M-CsPbBr3 SNWs to fabricate circularly polarized light (CPL) photodetectors, which exhibited an impressive photocurrent dissymmetry factor (gIph) of 0.75. In the field of spin light-emitting diodes (spin-LEDs), circularly polarized electroluminescence (CPEL) was accomplished by employing the SNWs as a dual-functional material that provides both chiral-induced spin selectivity (CISS) and CPL emission capabilities.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"57 14 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713518","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

Degradable Alternating Copolymers from Living Radical Copolymerization of Natural Levoglucosenone and Dienes

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 DOI: 10.1021/jacs.5c02397

Lianqian Wu, Hongsik Kim, Tae-Lim Choi

引用次数: 0

Inner–Outer Sheath Synergistic Shielding of Polysulfides in Asymmetric Solvent-Based Electrolytes for Stable Sodium–Sulfur Batteries

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 DOI: 10.1021/jacs.4c18374

Weiqi Yao, Min-Hao Pai, Arumugam Manthiram

{"title":"Inner–Outer Sheath Synergistic Shielding of Polysulfides in Asymmetric Solvent-Based Electrolytes for Stable Sodium–Sulfur Batteries","authors":"Weiqi Yao, Min-Hao Pai, Arumugam Manthiram","doi":"10.1021/jacs.4c18374","DOIUrl":"https://doi.org/10.1021/jacs.4c18374","url":null,"abstract":"Room-temperature sodium–sulfur (RT Na–S) batteries are garnering interest owing to their high theoretical energy density and low cost. However, the notorious shuttle behavior of sodium polysulfides (NaPS) and uncontrollable dendrite growth lead to the poor cycle stability of RT Na–S cells. In this work, we report the use of 1,2-dimethoxypropane (DMP) and 1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl ether (TFTFE) as inner solvent and outer diluent, respectively, in a localized high-concentration electrolyte system. Impressively, the asymmetric DMP as the inner solvent, introduced to replace the conventional solvent 1,2-dimethoxyethane (DME), shields NaPS effectively from incorporation into the inner solvation structure due to the extra methyl groups in the molecular structure. Furthermore, the TFTFE diluent, which contains electron-withdrawing perfluoro segments (−CF3– and −CF2−), exhibits significantly low solvation power. Consequently, the outer sheath TFTFE diluent further minimizes NaPS dissolution, thereby enhancing the cycle stability. This inner–outer sheath synergistic effect leads to the formation of highly effective cathode-electrolyte interphase (CEI) and solid-electrolyte interphase (SEI) layers simultaneously, significantly alleviating the shuttle effect and reducing the side reactions between NaPS and sodium metal. Remarkably, the Na–S cells with the designed electrolyte present long-cycling reversibility with 530 mAh g–1 over 600 cycles at a C/2 rate and a low capacity decay rate of 0.077% per cycle. This study provides a profound understanding of the electrolyte structure involving NaPS and offers a firm basis for the rational design of electrolytes for rechargeable metal–sulfur battery systems.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"86 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703085","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

Subnanometric Nickel Phosphide Heteroclusters with Highly Active Niδ+–Pδ− Pairs for Nitrate Reduction toward Ammonia

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 DOI: 10.1021/jacs.5c01455

Qi Hu, Chunyan Shang, Xinbao Chen, Shuai Qi, Qihua Huo, Hengpan Yang, Chuanxin He

{"title":"Subnanometric Nickel Phosphide Heteroclusters with Highly Active Niδ+–Pδ− Pairs for Nitrate Reduction toward Ammonia","authors":"Qi Hu, Chunyan Shang, Xinbao Chen, Shuai Qi, Qihua Huo, Hengpan Yang, Chuanxin He","doi":"10.1021/jacs.5c01455","DOIUrl":"https://doi.org/10.1021/jacs.5c01455","url":null,"abstract":"The development of efficient electrocatalysts for the neutral nitrate reduction reaction (NO3–RR) toward ammonia (NH3) is essential to address the environmental issues caused by NO3– but remains considerably challenging owing to the sluggish reaction kinetics of NO3–RR in neutral media. Herein, we report subnanometric heteroclusters with strongly coupled nickel–phosphorus (Ni–P) dual-active sites as electrocatalysts to boost the neutral NO3–RR. Experimental and theoretical results reveal that the subnanometric feature of Ni–P heteroclusters promotes the electron transfer from Ni to P, generating Niδ+–Pδ− active pairs, in which Niδ+ species are highly active for the NO3–RR and Pδ− tunes the interfacial water hydrogen bonding network to promote the water dissociation step and accelerate proton transfer during the NO3–RR. Consequently, in the neutral NO3–RR, Ni–P heteroclusters exhibit a large NH3 yield rate of 0.61 mmol h–1 cm–2 at −0.8 V versus reversible hydrogen electrode, which is 2.8- and 3.3-fold larger than those on Ni–P nanoparticles and Ni clusters, respectively, and the generated NH3 exists as NH4+ in electrolytes. This study offers an efficient approach to boosting electrocatalytic reactions with multiple intermediates by designing subnanometric heteroclusters with strongly coupled active sites.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"6 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713728","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

Manganese-Driven Plasmid Nanofibers Formed In Situ for Cancer Gene Delivery and Metalloimmunotherapy.

IF 14.4 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 Epub Date: 2025-03-10 DOI: 10.1021/jacs.4c18511

Jiexin Li, Ruiqi Yang, Chen Zhang, Jonathan F Lovell, Yumiao Zhang

{"title":"Manganese-Driven Plasmid Nanofibers Formed In Situ for Cancer Gene Delivery and Metalloimmunotherapy.","authors":"Jiexin Li, Ruiqi Yang, Chen Zhang, Jonathan F Lovell, Yumiao Zhang","doi":"10.1021/jacs.4c18511","DOIUrl":"10.1021/jacs.4c18511","url":null,"abstract":"While nucleic-acid-based cancer vaccines hold therapeutic potential, their limited immunogenicity remains a challenge due in part to the low efficiency of cytoplasmic delivery caused by lysosomal entrapment. In this work, we found that plasmids encoding both an antigen and a STING agonist protein adjuvant can self-assemble into coordination nanofibers, triggered by manganese ions. We developed a strategy to construct a DNA vaccine, termed MnO2-OVA-CDA-mem, formed by the coencapsulation of manganese dioxide (MnO2), an antigen-expressing plasmid (encoding ovalbumin, OVA), and an adjuvant enzyme-expressing plasmid (encoding STING agonist, CDA) within dendritic cell (DC) membranes. Upon uptake into acidic lysosomes, Mn2+ released from MnO2 triggered the nucleic acids to undergo a morphological change from nanospheres (∼180 nm diameter) to nanofibers (∼1 μm length), resulting in an increase in mechanical strength by about 9-fold and consequently lysosomal membrane disruption. The antigen OVA and adjuvants Mn2+ and CDA in the cytoplasm triggered strong DC activation and antigen-specific CD8+ T cell metalloimmune responses, significantly inhibiting the growth of B16-OVA tumors and inducing long-term immune memory. Altogether, MnO2-OVA-CDA-mem holds potential as a platform for nucleic acid antigen and adjuvant delivery using an in situ self-assembly strategy in a metal-driven, stimulus-responsive, and programmable manner for cancer metalloimmunotherapy.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":"10504-10518"},"PeriodicalIF":14.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595891","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

Highly Specific Miniaturized Fluorescent Monoacylglycerol Lipase Probes Enable Translational Research.

IF 14.4 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 Epub Date: 2025-03-10 DOI: 10.1021/jacs.4c15223

Axel Hentsch, Mónica Guberman, Silke Radetzki, Sofia Kaushik, Mirjam Huizenga, Yingfang He, Jörg Contzen, Bernd Kuhn, Jörg Benz, Maria Schippers, Jerome Paul, Lea Leibrock, Ludovic Collin, Matthias Wittwer, Andreas Topp, Fionn O'Hara, Dominik Heer, Remo Hochstrasser, Julie Blaising, Jens P von Kries, Linjing Mu, Mario van der Stelt, Philipp Mergenthaler, Noa Lipstein, Uwe Grether, Marc Nazaré

{"title":"Highly Specific Miniaturized Fluorescent Monoacylglycerol Lipase Probes Enable Translational Research.","authors":"Axel Hentsch, Mónica Guberman, Silke Radetzki, Sofia Kaushik, Mirjam Huizenga, Yingfang He, Jörg Contzen, Bernd Kuhn, Jörg Benz, Maria Schippers, Jerome Paul, Lea Leibrock, Ludovic Collin, Matthias Wittwer, Andreas Topp, Fionn O'Hara, Dominik Heer, Remo Hochstrasser, Julie Blaising, Jens P von Kries, Linjing Mu, Mario van der Stelt, Philipp Mergenthaler, Noa Lipstein, Uwe Grether, Marc Nazaré","doi":"10.1021/jacs.4c15223","DOIUrl":"10.1021/jacs.4c15223","url":null,"abstract":"Monoacylglycerol lipase (MAGL) is the pivotal catabolic enzyme responsible for signal termination in the endocannabinoid system. Inhibition of MAGL offers unique advantages over the direct activation of cannabinoid receptors in treating cancer, metabolic disorders, and inflammatory diseases. Although specific fluorescent molecular imaging probes are commonly used for the real-time analysis of the localization and distribution of drug targets in cells, they are almost invariably composed of a linker connecting the pharmacophore with a large fluorophore. In this study, we have developed miniaturized fluorescent probes targeting MAGL by incorporating a highly fluorescent boron-dipyrromethene (BODIPY) moiety into the inhibitor structure that interacts with the MAGL active site. These miniaturized fluorescent probes exhibit favorable drug-like properties such as high solubility and permeability, picomolar potency for MAGL across various species, and high cell selectivity and specificity. A range of translational investigations were conducted, including cell-free fluorescence polarization assays, fluorescence-activated cell sorting analysis, and confocal fluorescence microscopy of live cancer cells, live primary neurons, and human-induced pluripotent stem cell-derived brain organoids. Furthermore, the application of red-shifted analogs or 18F positron emission labeling illustrated the significant versatility and adaptability of the fluorescent ligands in various experimental contexts.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":"10188-10202"},"PeriodicalIF":14.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Quantum Coulombic Interactions Mediate Free Radical Control in Radical SAM Viperin/RSAD2

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 DOI: 10.1021/jacs.5c00572

M. Hossein Khalilian, Gino A. DiLabio

{"title":"Quantum Coulombic Interactions Mediate Free Radical Control in Radical SAM Viperin/RSAD2","authors":"M. Hossein Khalilian, Gino A. DiLabio","doi":"10.1021/jacs.5c00572","DOIUrl":"https://doi.org/10.1021/jacs.5c00572","url":null,"abstract":"There are thousands of radical S-adenosylmethionine (rSAM) enzymes capable of catalyzing over 80 distinct reactions, yet their use in biotechnological applications is limited, primarily due to a lack of understanding of how these enzymes control highly reactive radical intermediates. Here, we show that little-known quantum Coulombic interactions are, in part, responsible for free radical control in rSAM enzyme Viperin/RSAD2, one of the few radical SAM enzymes expressed in humans. Using molecular dynamics and high-level extensive multistate broken-symmetry quantum mechanical/molecular mechanics calculations (QM/MM), we elucidated both the mechanism and radical control in catalysis, identifying a key step characterized by the formation of an unusual metastable deprotonated ribose radical intermediate. This intermediate is thermodynamically stabilized by spin-charge exchange–correlation interactions─a quantum Coulombic effect. The magnitude of this stabilization is such that the radical displays acidity two to six pKa units lower than that of closed-shell ribose. Given the omnipresence of charges in biological systems, these interactions potentially represent a universal mechanism for stabilizing and controlling highly reactive radical intermediates across radical enzymes, opening new avenues for enzymatic engineering and biotechnological applications.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"215 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703084","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