Journal of the American Chemical Society最新文献_第8页

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

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

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

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

Methanol to Olefins (MTO): Understanding and Regulating Dynamic Complex Catalysis

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-26 DOI: 10.1021/jacs.4c12145

Shanfan Lin, Hua Li, Peng Tian, Yingxu Wei, Mao Ye, Zhongmin Liu

{"title":"Methanol to Olefins (MTO): Understanding and Regulating Dynamic Complex Catalysis","authors":"Shanfan Lin, Hua Li, Peng Tian, Yingxu Wei, Mao Ye, Zhongmin Liu","doi":"10.1021/jacs.4c12145","DOIUrl":"https://doi.org/10.1021/jacs.4c12145","url":null,"abstract":"The research and development of methanol conversion into hydrocarbons have spanned more than 40 years. The past four decades have witnessed mutual promotion and successive breakthroughs in both fundamental research and industrial process development of methanol to olefins (MTO), demonstrating that MTO is an extremely dynamic, complex catalytic system. This Perspective summarizes the endeavors and achievements of the Dalian Institute of Chemical Physics, Chinese Academy of Sciences, in the continuous study of reaction mechanisms and process engineering of the dynamic, complex MTO reaction system. It elucidates fundamental chemical issues concerning the essence of the dynamic evolution of the MTO reaction and the cross-talk mechanisms among diffusion, reaction, and catalyst (coke modification), which are crucial for technology development and process optimization. By integrating the chemical principles, the reaction-diffusion model, and coke formation kinetics of MTO, a mechanism- and model-driven modulation of industrial processes has been achieved. The acquisition of a deepening understanding in chemistry and engineering has facilitated the continuous optimization and upgrading of MTO catalysts and processes.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"19 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713724","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

Expression of Human β3GalT5–1 in Insect Cells as Active Glycoforms for the Efficient Synthesis of Cancer-Associated Globo-Series Glycans

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-03-25 DOI: 10.1021/jacs.4c11723

Chih-Chuan Kung, Jennifer M. Lo, Kuo-Shiang Liao, Chung-Yi Wu, Li-Chun Cheng, Cinya Chung, Tsui-Ling Hsu, Che Ma, Chi-Huey Wong

{"title":"Expression of Human β3GalT5–1 in Insect Cells as Active Glycoforms for the Efficient Synthesis of Cancer-Associated Globo-Series Glycans","authors":"Chih-Chuan Kung, Jennifer M. Lo, Kuo-Shiang Liao, Chung-Yi Wu, Li-Chun Cheng, Cinya Chung, Tsui-Ling Hsu, Che Ma, Chi-Huey Wong","doi":"10.1021/jacs.4c11723","DOIUrl":"https://doi.org/10.1021/jacs.4c11723","url":null,"abstract":"The globo-series glycosphingolipids (GSLs) are unique glycolipids exclusively expressed on the cell surface of various types of cancer and have been used as targets for the development of cancer vaccines and therapeutics. A practical enzymatic method has been developed for the synthesis of globo-series glycans, where the conversion of Gb4 to Gb5 (SSEA-3) glycan based on the microbial galactosyltransferase LgtD is relatively inefficient compared to other steps. To improve the efficiency, we explored the two human galactosyltransferase (β3GalT5) isozymes in cancer cells for this reaction and found that isozyme 1 (β3GalT5–1) is more active than isozyme 2 (β3GalT5–2). We then identified a common soluble domain of the two β3GalT5 isozymes as a candidate and evaluated the activity and substrate specificity of the glycosylated and nonglycosylated glycoforms. The glycoforms expressed in Sf9 cells were selected, and a site-specific alanine scan was performed to identify S66A β3GalT5 variant with 10-fold more efficiency than LgtD for the synthesis of globo-series glycans. The X-ray structure of β3GalT5–1 was determined for molecular modeling, and the result together with kinetic data were used to rationalize the improvement in catalysis.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"13 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695866","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