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Direct Preparation of Site-Specific Antibody-Drug Conjugates with Unpurified Antibodies in Culture Medium.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-28 DOI: 10.1002/cbic.202401082
Mengru Lu, Yue Zeng, Jiaying Hang, Wei Shi, Wei Huang, Feng Tang
{"title":"Direct Preparation of Site-Specific Antibody-Drug Conjugates with Unpurified Antibodies in Culture Medium.","authors":"Mengru Lu, Yue Zeng, Jiaying Hang, Wei Shi, Wei Huang, Feng Tang","doi":"10.1002/cbic.202401082","DOIUrl":"10.1002/cbic.202401082","url":null,"abstract":"<p><p>In comparison with traditional chemotherapeutic drugs, antibody-drug conjugates (ADCs) have been extensively employed in cancer therapy due to their high selectivity and low systemic toxicity. However, the structural complexity of ADCs makes its preparation process more intricate and time-consuming. Conventional ADC production involves multistep purification processes, which significantly increase the costs. Herein, an approach for the direct preparation of site-specific ADCs in an antibody expression system that is derived from the reported K248 site-specific modification technology is demonstrated. This strategy requires only a single purification step to obtain site-specific ADCs, thereby greatly shortening the preparation cycle of ADCs. The preparation of site-specific ADCs in the expression system of Sacituzumab is successfully achieved. The resulting ADCs exhibited comparable physicochemical properties and activities to those obtained through the conventional two-step purification strategy. The approach demonstrates high compatibility with various linkers and antibodies, offering a streamlined methodology for the preparation of site-specific ADCs.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2401082"},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Self-Assembly of Cholane-Phenanthrene-Cholane Trimers for Light-Harvesting Supramolecular Systems.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-28 DOI: 10.1002/cbic.202500121
Edouard Ehret, Ioan Iacovache, Simon M Langenegger, Benoît Zuber, Robert Häner
{"title":"Self-Assembly of Cholane-Phenanthrene-Cholane Trimers for Light-Harvesting Supramolecular Systems.","authors":"Edouard Ehret, Ioan Iacovache, Simon M Langenegger, Benoît Zuber, Robert Häner","doi":"10.1002/cbic.202500121","DOIUrl":"https://doi.org/10.1002/cbic.202500121","url":null,"abstract":"<p><p>The self-assembly of two isomeric amphiphilic cholane-phenanthrene-cholane trimers and the light-harvesting properties of the formed supramolecular assemblies in aqueous medium are presented. Distinct differences in the supramolecular nanostructures were observed based on the type of phenanthrene isomer used, as well as on the cooling rate applied during the thermal self-assembly process. A fast cooling rate resulted in the formation of 2D objects (nanosheets) with both trimers. In contrast, a slow cooling process resulted in the observation of 3D objects, with worm-like nanostructures for the self-assembled 3,6-disubstituted phenanthrene trimer and nanotubes for the 2,7-isomer. Upon doping with an acceptor chromophore, the supramolecular phenanthrene assemblies demonstrated efficient energy transfer. The presence of small quantities (6%) of a pyrene acceptor resulted in a five-fold increase in the quantum yield compared to the phenanthrene trimer alone, highlighting their potential as artificial light-harvesting complexes. This work underscores the versatility of amphiphilic phenanthrene derivatives as building blocks for light-harvesting supramolecular systems.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500121"},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interdomain Coordination Determines Polyketide Extender Unit Specificity in UK-2A Biosynthesis.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-27 DOI: 10.1002/cbic.202401050
Mengmeng Zheng, Wan Zhang, Zhi Lin, Lei Li, Zixin Deng, Xudong Qu
{"title":"Interdomain Coordination Determines Polyketide Extender Unit Specificity in UK-2A Biosynthesis.","authors":"Mengmeng Zheng, Wan Zhang, Zhi Lin, Lei Li, Zixin Deng, Xudong Qu","doi":"10.1002/cbic.202401050","DOIUrl":"10.1002/cbic.202401050","url":null,"abstract":"<p><p>Controlling the incorporation of extender units is a key strategy for manipulating polyketide scaffolds. Current understanding suggests that extender unit incorporation by modular polyketide synthase (PKS) is primarily regulated by acyltransferase domains, along with ketosynthase, ketoreductase, and thioesterase domains. In this study, the mechanism is investigated underlying the specific incorporation of the benzyl side chain at the C7 position of UK-2A, both in vivo and in vitro. These findings reveal that the incorporation of the benzylmalonyl-CoA extender unit is governed by interdomain coordination across the entire PKS module, rather than being controlled by individual domains. These results challenge previous recognition and offer new insights for the future engineering of polyketides.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2401050"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular Tweezers for Biomimetic Recognition of Carbohydrates.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-27 DOI: 10.1002/cbic.202500123
Francesco Milanesi, Naufia Mohamedzakaria Shibinasbarveen, Stefano Roelens, Oscar Francesconi
{"title":"Molecular Tweezers for Biomimetic Recognition of Carbohydrates.","authors":"Francesco Milanesi, Naufia Mohamedzakaria Shibinasbarveen, Stefano Roelens, Oscar Francesconi","doi":"10.1002/cbic.202500123","DOIUrl":"https://doi.org/10.1002/cbic.202500123","url":null,"abstract":"<p><p>Molecular recognition of biomolecules by means of synthetic receptors is a key topic with several potential applications, which must face the challenge of recognizing relatively large guests in an aqueous medium. Due to their open cavity, molecular tweezers are promising architectures for this purpose that have already shown interesting recognition properties with lipids, nucleic acids, and proteins, thereby eliciting biological activities. Carbohydrates, assembled within glycans, are polar biomolecules of high structural complexity that are particularly difficult to be effectively recognized in water. Notably, in addition to reports on more widely explored structures, significant advances have been achieved exploiting the structural peculiarity of tweezer receptors. In this review a selection of some emblematic examples from the literature of molecular tweezers, cleft and clips targeting carbohydrates is presented, together with a discussion of the advantages and limitations of this type of architecture.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500123"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","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 Metal-Ion Binding Properties of Duplexes Containing Thymine Analogs with 1,2-Diamine Groups.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-27 DOI: 10.1002/cbic.202500017
Takahiro Atsugi, Shoji Fujiwara, Jiro Kondo, Akira Ono
{"title":"Synthesis and Metal-Ion Binding Properties of Duplexes Containing Thymine Analogs with 1,2-Diamine Groups.","authors":"Takahiro Atsugi, Shoji Fujiwara, Jiro Kondo, Akira Ono","doi":"10.1002/cbic.202500017","DOIUrl":"10.1002/cbic.202500017","url":null,"abstract":"<p><p>Thymidine analogue with a 1,2-diamino side chain at the 3N position is synthesized and converted into an amidite unit for oligonucleotide synthesis. It is used for preparing oligonucleotides containing a 1,2-diamino side chain as X residue. Thermal denaturation studies are performed on a duplex containing an X-X pair in the presence and absence of metal ions. Among various metal ions used in this research, Cd(II), Co(II), Cu(II), Ni(II), and Zn(II) ions increased the duplex stability. The results prove the new strategy to design metallo-base pairs containing various metal ions.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500017"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Leaf-like nanostructures self-assembled by silver-coordinated photosensitizers as collaborative antimicrobial agents.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-27 DOI: 10.1002/cbic.202500025
Xiaoxue Fan, Ran An, Shibo Lv, Feng Chen, Dapeng Liu, Fengling Song
{"title":"Leaf-like nanostructures self-assembled by silver-coordinated photosensitizers as collaborative antimicrobial agents.","authors":"Xiaoxue Fan, Ran An, Shibo Lv, Feng Chen, Dapeng Liu, Fengling Song","doi":"10.1002/cbic.202500025","DOIUrl":"https://doi.org/10.1002/cbic.202500025","url":null,"abstract":"<p><p>This research introduces an innovative approach to addressing bacterial infections in wounds using leaf-like nanostructures, which are self-assembled via coordination between the photosensitizer Cz-BTZ-mPy and silver ions. These nanostructures combine photosensitizer-generated singlet oxygen with silver's antibacterial effects, synergistically promoting wound healing. When incorporated into a Carbopol 941 hydrogel matrix, these nanostructures achieve near-total bacterial eradication (0.04% survival) while accelerating wound healing and tissue regeneration in a mouse model. This dual-functional mechanism allows the nanostructures to perform exceptionally well against Gram-positive and Gram-negative bacteria, even in biofilm environments, where conventional strategies solely on individual components often fail.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500025"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Profiling Serine Hydrolases in the Leishmania Host-Pathogen Interactome Using Cell-Permeable Activity-Based Fluorophosphonate Probes.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-27 DOI: 10.1002/cbic.202500160
Jaime A Isern, Exequiel O J Porta, Karunakaran Kalesh, Zisis Koutsogiannis, Davide Cazzola, Ehmke Pohl, Paul Denny, Patrick G Steel
{"title":"Profiling Serine Hydrolases in the Leishmania Host-Pathogen Interactome Using Cell-Permeable Activity-Based Fluorophosphonate Probes.","authors":"Jaime A Isern, Exequiel O J Porta, Karunakaran Kalesh, Zisis Koutsogiannis, Davide Cazzola, Ehmke Pohl, Paul Denny, Patrick G Steel","doi":"10.1002/cbic.202500160","DOIUrl":"https://doi.org/10.1002/cbic.202500160","url":null,"abstract":"<p><p>Leishmaniasis, a vector borne neglected tropical disease, caused by the protozoan parasite Leishmania, is a major global public health challenge with millions of new cases annually. Treatment of leishmaniasis is difficult for many reasons including a multiple life-cycle stages, involving both an infective insect vector form, the promastigote, and a disease causing intracellular mammalian host form, the amastigote, and increasing drug-tolerance that are all linked by the interplay between parasite and host. We employed activity-based protein profiling (ABPP) using new cell-permeable fluorophosphonate probes to explore serine hydrolases (SHs) in Leishmania mexicana with subsequent analysis enabled by secondary reaction with an affinity reagent. Importantly, these cell-permeable probes can access all life-cycle stages including the disease-critical intramacrophage amastigote. Probe efficacy is a combination of both target engagement and subsequent accessibility to the affinity agent. Fourteen SHs, including peptidases and lipases, were identified in the L. mexicana proteome with comparative profiling of different parasite life-stages revealing significant changes in SH activity across the life-cycle stages. This intra-cellular ABPP approach provides insights into the host-parasite interactome demonstrating that SHs function as important virulence factors with Z-Pro-Prolinal, a known prolyloligopeptidase inhibitor, being able to reduce parasite infectivity in the macrophage by altering multiple SH targets.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500160"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Study on the Asymmetric Synthesis of Chiral 3,3,3-Trifluoro-2-Hydroxypropanoic Acids by Lactate Dehydrogenase.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-27 DOI: 10.1002/cbic.202500047
Jingfei Wu, Aem Nuylert, Misako Iwaki, Shinsuke Miki, Yasuhisa Asano
{"title":"Study on the Asymmetric Synthesis of Chiral 3,3,3-Trifluoro-2-Hydroxypropanoic Acids by Lactate Dehydrogenase.","authors":"Jingfei Wu, Aem Nuylert, Misako Iwaki, Shinsuke Miki, Yasuhisa Asano","doi":"10.1002/cbic.202500047","DOIUrl":"https://doi.org/10.1002/cbic.202500047","url":null,"abstract":"<p><p>Chiral 3,3,3-trifluoro-2-hydroxypropanoic acid (3,3,3-trifluorolactic acid, TFLA), which possesses two significant functional groups, is a versatile intermediate in pharmaceutical and material synthesis. A feasible strategy for producing both the enantiomers of chiral TFLAs involves reduction of the corresponding pyruvate using lactate dehydrogenases (LDHs). In this study, ldh genes encoding l-LDHs from animals and d/l-LDHs from lactic acid bacteria are cloned and all the recombinant LDHs are successfully expressed with a histidine tag in Escherichia coli BL21 (DE3). To achieve cofactor regeneration, a nicotinamide adenine dinucleotide regeneration system is constructed using formate dehydrogenase from Candida boidinii. Chiral TFLA is synthesized from 3,3,3-trifluoro-2-oxopropionic acid (trifluoropyruvic acid, TFPy) with good yields and excellent stereoselectivity, catalyzed by lactate dehydrogenases and formate dehydrogenase. Under optimized biocatalytic conditions, highly active d-LmLDH from Leuconostoc mesenteroides and chicken l-LDH from Gallus are screened for their ability to completely convert 0.5 m TFPy to produce optically pure (S)-TFLA and (R)-TFLA with enantiomeric excess >99.5% within 6 h, respectively. Molecular docking simulations investigate the catalytic mechanisms of selected d-LDH and l-LDH, revealing their activity and stereoselectivity toward CF<sub>3</sub>-containing TFPy.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500047"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lanthanide-Doped Upconversion Nanoparticles for Single-Particle Imaging.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-26 DOI: 10.1002/cbic.202400942
Huan Ling, Wenrui Zhang, Yunxiang Zhang, Jie Shen, Qian Liu
{"title":"Lanthanide-Doped Upconversion Nanoparticles for Single-Particle Imaging.","authors":"Huan Ling, Wenrui Zhang, Yunxiang Zhang, Jie Shen, Qian Liu","doi":"10.1002/cbic.202400942","DOIUrl":"https://doi.org/10.1002/cbic.202400942","url":null,"abstract":"<p><p>Lanthanide-doped upconversion nanoparticles (UCNPs) have recently demonstrated great promise in single-particle imaging (SPI) due to their exceptional photostability and minimal background fluorescence. However, their relatively dim brightness has posed a significant barrier to wider adoption in SPI applications. This review highlights recent advances in the application of UCNPs for SPI, focusing on strategies to enhance their brightness and reduce quenching effects in aqueous environments. Additionally, it summarizes the latest progress in employing UCNPs for single-particle tracking and super-resolution imaging, underscoring their potential in biomedical research. Finally, the review outlines current challenges and future directions in this field.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400942"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bioactive specialized metabolites from Staphylococcus: diversity, biosynthesis and biotechnological potential.
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2025-03-26 DOI: 10.1002/cbic.202500105
Ruben Maes, Mahmoud Naser Aldine, Hans Gerstmans, Chris Michiels, Joleen Masschelein
{"title":"Bioactive specialized metabolites from Staphylococcus: diversity, biosynthesis and biotechnological potential.","authors":"Ruben Maes, Mahmoud Naser Aldine, Hans Gerstmans, Chris Michiels, Joleen Masschelein","doi":"10.1002/cbic.202500105","DOIUrl":"https://doi.org/10.1002/cbic.202500105","url":null,"abstract":"<p><p>Staphylococci are a heterogeneous group of bacteria capable of colonizing diverse ecological niches and adopting a wide variety of lifestyles. While several strains are known as notorious, multidrug-resistant human pathogens, others are harmless inhabitants of soil, water and food products, or beneficial members of the skin microbiota. To survive and remain competitive under challenging environmental conditions, staphylococci have evolved the ability to assemble and secrete a diverse range of ribosomally synthesized and post-translationally modified peptides, nonribosomal peptides, terpenes, siderophores and other specialized metabolites with antibiotic, immunomodulating and metal chelating activities. In this review, we provide an overview of the bioactive metabolite arsenal of staphylococci with a focus on their biosynthetic pathway, mode of action and industrial application potential. We also highlight unexplored natural product biosynthetic pathways in staphylococci, along with strategies to access this hidden potential.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500105"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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