Bioconjugate Chemistry最新文献_第2页

The Journey and Modes of Action of Therapeutic Nanomaterials in Cells. 治疗性纳米材料在细胞中的历程和作用模式。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-04-11 DOI: 10.1021/acs.bioconjchem.4c00584

Célia Sahli, Kenry

{"title":"The Journey and Modes of Action of Therapeutic Nanomaterials in Cells.","authors":"Célia Sahli, Kenry","doi":"10.1021/acs.bioconjchem.4c00584","DOIUrl":"10.1021/acs.bioconjchem.4c00584","url":null,"abstract":"Over past decades, a wide range of nanomaterials have been synthesized and exploited to augment the efficacy and biocompatibility of disease theranostics and nanomedicine. The unique physicochemical properties of nanomaterials, such as high specific surface area, tunable size and shape, and versatile surface chemistry, enable the controlled modulation of nanomaterial-biosystem interactions and, consequently, more precise interventions, particularly at the cellular level. The selective modulation of nanomaterial-cell interactions can be leveraged to regulate cellular internalization, intracellular trafficking and localization, and cellular clearance of nanomaterials to enhance the disease therapeutic efficacy and minimize potential cytotoxicity. Herein, we provide an overview of our recent understanding of the journey and modes of action of therapeutic nanomaterials in cells. Specifically, we highlight the various pathways of cellular internalization, trafficking, and excretion of these nanomaterials. The different modes of action of therapeutic nanomaterials, especially controlled release and delivery, photothermal and photodynamic effects, and immunomodulation, are also discussed. We conclude our review by offering some perspectives on the current challenges and potential opportunities in this field.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"914-929"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Elucidating Critical Factors of Internalization and Drug Release of Antibody-Drug Conjugates (ADCs) Using Kinetic Parameters Evaluated by a Novel Tool Named TORCH. 利用新的工具TORCH评价抗体-药物偶联物（adc）的动力学参数来阐明其内化和药物释放的关键因素。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-05-06 DOI: 10.1021/acs.bioconjchem.4c00579

Stanley Sweeney-Lasch, Marie Quillmann, Jens Hannewald, Stephan Dickgiesser, Nicolas Rasche, Min Shan, Carl Deutsch, Stefan Hecht, Jan Anderl, Harald Kolmar, Birgit Piater

{"title":"Elucidating Critical Factors of Internalization and Drug Release of Antibody-Drug Conjugates (ADCs) Using Kinetic Parameters Evaluated by a Novel Tool Named TORCH.","authors":"Stanley Sweeney-Lasch, Marie Quillmann, Jens Hannewald, Stephan Dickgiesser, Nicolas Rasche, Min Shan, Carl Deutsch, Stefan Hecht, Jan Anderl, Harald Kolmar, Birgit Piater","doi":"10.1021/acs.bioconjchem.4c00579","DOIUrl":"10.1021/acs.bioconjchem.4c00579","url":null,"abstract":"During the past decade, antibody-drug conjugates (ADCs) have emerged as new drugs in cancer therapy with 15 ADCs already approved such as Kadcyla, Enhertu, and Adcetris. ADCs contain a cytotoxic drug that is linked to an antibody, allowing for specific delivery of the warhead to tumor cells. Typically, the antibody targets a tumor-specific antigen expressed on the cell surface. After the internalization of ADCs into cells, the linker is often cleaved by enzymes in the lysosomal compartment of the cell, releasing the warhead and thereby allowing for its interaction with, for example, the DNA or the tubulin cytoskeleton, which finally leads to cell death. Consequently, binding, internalization, and drug release are key attributes for the efficacy of ADCs. Here, we describe a novel molecule named TORCH (Turn On after Release by CatHepsins) that contains a fluorescence quencher system that is separated by a cathepsin B-cleavable linker. When conjugated to an antibody, the TORCH molecule allows one to gain valuable insights on the internalization and drug release of ADCs. While we cannot exclude the influence of other factors such as receptor recycling, we have found that the receptor density is directly related to the amount of payload released intracellularly, meaning that the internalization per receptor is very similar for all investigated antibodies and cell lines.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"945-959"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Novel Approaches to Label the Surface of S. aureus with DBCO for Click Chemistry-Mediated Deposition of Sensitive Cargo. 用DBCO标记金黄色葡萄球菌表面的新方法用于点击化学介导的敏感货物沉积。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 DOI: 10.1021/acs.bioconjchem.4c00575

Tsvetelina H Baryakova, Chia-Chien Hsu, Laura Segatori, Kevin J McHugh

{"title":"Novel Approaches to Label the Surface of S. aureus with DBCO for Click Chemistry-Mediated Deposition of Sensitive Cargo.","authors":"Tsvetelina H Baryakova, Chia-Chien Hsu, Laura Segatori, Kevin J McHugh","doi":"10.1021/acs.bioconjchem.4c00575","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00575","url":null,"abstract":"The strain-promoted alkyne-azide cycloaddition (SPAAC) reaction can be used to modify the surface of bacteria for a variety of applications including drug delivery, biosensing, and imaging. This is usually accomplished by first installing a small azide group within the peptidoglycan and then delivering exogenous cargo (e.g., a protein or nanoparticle) modified with a cyclooctyne group, such as dibenzocyclooctyne (DBCO), for in situ conjugation. However, DBCO is comparatively bulky and hydrophobic, increasing the propensity of some payloads to aggregate. In this study, we sought to invert this paradigm by exploring two novel strategies for incorporating DBCO into the peptidoglycan of Staphylococcus aureus and compared them to an established approach using DBCO-vancomycin. We demonstrate that DBCO-modified small molecules belonging to all three classes─a sortase peptide substrate (LPETG), two d-alanine derivatives, and vancomycin─can selectively label the S. aureus surface to varying degrees. In contrast to DBCO-vancomycin, the DBCO-d-alanine variants do not adversely affect the growth of S. aureus or lead to off-target labeling or toxicity in HEK293T or RAW 264.7 cells. Finally, we show that, unlike IgG3-Fc labeled with DBCO groups, IgG3-Fc labeled with azide groups is stable (i.e., remains water-soluble) under normal storage conditions, retains its ability to bind the immune receptor CD64, and can be successfully attached to the surface of DBCO-modified S. aureus. We believe that the labeling strategies explored herein will expand the paradigm of specific, nontoxic SPAAC-mediated labeling of the surface of S. aureus and other Gram-positive bacteria, opening the door for new applications using azide-modified cargo.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Mitigating Cannabidiol's Non-Selective Cytotoxicity via Subcellular Organelle Targeting: Exploring Mitochondrial Targeting Potential. 通过亚细胞细胞器靶向减轻大麻二酚的非选择性细胞毒性：探索线粒体靶向潜力。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-04-08 DOI: 10.1021/acs.bioconjchem.5c00012

Genglian Liu, Ru Li, Jingwei Gao, Cong Lin, Hongyuan Li, Yinghua Peng, Hongshuang Wang, Xiaohui Wang

{"title":"Mitigating Cannabidiol's Non-Selective Cytotoxicity via Subcellular Organelle Targeting: Exploring Mitochondrial Targeting Potential.","authors":"Genglian Liu, Ru Li, Jingwei Gao, Cong Lin, Hongyuan Li, Yinghua Peng, Hongshuang Wang, Xiaohui Wang","doi":"10.1021/acs.bioconjchem.5c00012","DOIUrl":"10.1021/acs.bioconjchem.5c00012","url":null,"abstract":"Cannabidiol (CBD), a phytocannabinoid from Cannabis sativa, is renowned for its nonpsychoactive properties and therapeutic potential. However, its clinical application is limited by nonselective cytotoxicity, affecting microglia, oligodendrocytes, and other cells. To address this, subcellular organelle-targeting strategies were explored to minimize off-target effects and enhance CBD's therapeutic index. Three organelle-specific conjugates targeting mitochondria, endoplasmic reticulum, and lysosomes were synthesized. Among these, the mitochondria-targeting triphenylphosphonium (TPP)-modified CBD conjugates demonstrated reduced cytotoxicity and enhanced anti-inflammatory activity. Further optimization identified a four-carbon ether chain linker (CBD-TPP-C4) that increased antineuroinflammatory activity by 3-fold and reduced cytotoxicity by 1.6-fold, compared to unmodified CBD. CBD-TPP-C4 also elevated mitochondrial ATP levels in vitro, improved mitochondrial morphology and locomotor function in Caenorhabditis elegans, and potentiated morphine analgesia in mice. These findings highlight subcellular targeting as a promising strategy to enhance CBD's safety and efficacy, paving the way for improved therapeutic applications.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"980-992"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Comparative Study of Click Handle Stability in Common Ligation Conditions. 常用结扎条件下点击手柄稳定性的比较研究。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-04-27 DOI: 10.1021/acs.bioconjchem.5c00095

Caitlin Fawcett, Joe Watson, Stephen Richards, Alfred E Doherty, Hikaru Seki, Elizabeth A Love, Charlotte H Coles, Diane M Coe, Craig Jamieson

{"title":"Comparative Study of Click Handle Stability in Common Ligation Conditions.","authors":"Caitlin Fawcett, Joe Watson, Stephen Richards, Alfred E Doherty, Hikaru Seki, Elizabeth A Love, Charlotte H Coles, Diane M Coe, Craig Jamieson","doi":"10.1021/acs.bioconjchem.5c00095","DOIUrl":"10.1021/acs.bioconjchem.5c00095","url":null,"abstract":"Click chemistry efficiently ligates molecular building blocks in a robust and high-yielding manner and has found major application in the rapid modification of important molecular actors in biological systems. However, the high reactivity of click handles often correlates with decreased stability, which presents a significant challenge in the practical application of these systems. In the current study, we describe a survey of the stability of commonly deployed click manifolds across a range of widely used ligation conditions. Incompatible click handle and ligation condition combinations are identified, with kinetic half-lives and side products of each undesired reaction determined, including the assessment of stability over extended periods and in a protein environment. This data set provides researchers with a roadmap to expediently determine the most appropriate click reaction conditions for any given bioorthogonal application, thus elevating the probability of success of procedures that utilize click chemistry.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1054-1065"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

In Silico-Driven THIOMAB Approach for Stable PROTAC Conjugates by Docking Payloads in Antibody Cavities. 通过对接有效载荷在抗体腔中稳定PROTAC偶联物的硅驱动THIOMAB方法。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-04-08 DOI: 10.1021/acs.bioconjchem.4c00588

Shiwei Song, Yahui Liu, Jiaqi Liu, Wanyi Tai

{"title":"In Silico-Driven THIOMAB Approach for Stable PROTAC Conjugates by Docking Payloads in Antibody Cavities.","authors":"Shiwei Song, Yahui Liu, Jiaqi Liu, Wanyi Tai","doi":"10.1021/acs.bioconjchem.4c00588","DOIUrl":"10.1021/acs.bioconjchem.4c00588","url":null,"abstract":"The heterobifunctional proteolysis targeting chimeras (PROTACs) are a class of emerging therapeutic modalities that enable selective degradation of target proteins in cells. As antibody payloads, they offer several advantages compared to conventional chemical toxins, such as catalytic nature, potent and long-lasting activity, and precise selectivity to avoid systemic toxicity. However, the relatively large size and high hydrophobicity of these chimeric payloads may result in challenging the stability of antibodies, which complicates the in vivo performance. In this work, we use the highly hydrophobic GNE-987 as model PROTAC to evaluate a THIOMAB approach for mitigating the conjugate's hydrophobicity while maintaining the therapeutic potency. We describe an in silico method to select the less hydrophobic site in an antibody and employ the stable tetrapeptide-aminomethoxy linker to conjugate the PROTAC payloads. The resulting degrader-antibody conjugate (J591 DAC) displays antigen-dependent BRD4 degradation and potent cytotoxic activity in PSMA-positive cancer cells. Finally, this DAC, bearing two highly hydrophobic PROTACs, also exhibits a long blood retention and strong antitumor efficacy in mouse models, likely owing to the homogeneous and stable conjugation from the THIOMAB approach. This work provides an example of the design and construction of antibody conjugates with highly hydrophobic payloads.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"960-970"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Carrier Free 1,2,3,4,6-O-Pentagalloylglucose Nanoparticles for Treatment of Acute Lung Injury. 无载体1,2,3,4,6- o -五五烯基葡萄糖纳米颗粒治疗急性肺损伤

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-05-08 DOI: 10.1021/acs.bioconjchem.5c00197

Qi Zhang, Ying Wang, Zixuan Yang, Zhiming Xin, Haohua Deng, Wei Chen

引用次数: 0

Glycosylation Modification Balances the Aqueous Solubility of Lipidated Peptides and Facilitates Their Biostability. 糖基化修饰平衡脂化肽的水溶性并促进其生物稳定性。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-04-09 DOI: 10.1021/acs.bioconjchem.5c00057

Guozhen Dong, Liyan Gong, Qianqian Zhang, Wenqing Yao, Yiying Shi, Zongwen Gu, Xianmin Yang, Xiang Gao, Yaning Zheng, Chuanliang Zhang

{"title":"Glycosylation Modification Balances the Aqueous Solubility of Lipidated Peptides and Facilitates Their Biostability.","authors":"Guozhen Dong, Liyan Gong, Qianqian Zhang, Wenqing Yao, Yiying Shi, Zongwen Gu, Xianmin Yang, Xiang Gao, Yaning Zheng, Chuanliang Zhang","doi":"10.1021/acs.bioconjchem.5c00057","DOIUrl":"10.1021/acs.bioconjchem.5c00057","url":null,"abstract":"Protein tyrosine phosphatase N1 (PTPN1) is a key regulator of insulin and leptin signaling pathways, making it an attractive therapeutic target for type 2 diabetes. Recent studies have identified fatty acid conjugated BimBH3 analogues as promising PTPN1 inhibitors with antidiabetic potential. Peptide therapeutics have proven successful in the treatment of a wide range of medical conditions, yet challenges such as poor aqueous solubility, proteolytic degradation, and limited bioavailability still hinder their clinical application. In this study, we developed a series of novel BimBH3 peptide analogues through dual modifications involving fatty acid lipidation and glycosylation to address these limitations. These modifications significantly improved the peptides' solubility, proteolytic stability, and plasma half-life while preserving potent PTPN1 inhibitory activity, which is essential for enhancing insulin signaling in type 2 diabetes treatment. Among the analogues, compound L3 exhibited the most balanced profile, with an aqueous solubility increase over 10-fold, a half-life extension in rat plasma of 9.92-fold compared to the lead compound, and an IC50 of 0.78 μM against PTPN1. In vivo studies further demonstrated L3's efficacy in lowering blood glucose levels in mice. This study demonstrates the utility of glycosylation in overcoming the solubility and stability challenges associated with lipidated peptides. The optimized analogue L3 could serve as a proof of concept for developing novel long-acting PTPN1 inhibitors.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1004-1012"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

In Vivo Interrogation of Cell-Penetrating Peptide Function: Accumulation in Tumors and the Potential as a Specific PET Probe. 细胞穿透肽功能的体内研究：肿瘤中的积累和作为特异PET探针的潜力。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-04-09 DOI: 10.1021/acs.bioconjchem.5c00128

Zhan Si, Lulu Tian, Hongxin Zhou, Jiasheng Lin, Jun Zhou

{"title":"In Vivo Interrogation of Cell-Penetrating Peptide Function: Accumulation in Tumors and the Potential as a Specific PET Probe.","authors":"Zhan Si, Lulu Tian, Hongxin Zhou, Jiasheng Lin, Jun Zhou","doi":"10.1021/acs.bioconjchem.5c00128","DOIUrl":"10.1021/acs.bioconjchem.5c00128","url":null,"abstract":"We aimed to evaluate the biodistribution and specificity of 68Ga-DOTA-TAT and RHO-TAT using MGC-803 and HT-29 tumor cells as well as tumor-xenografted nude mice and to demonstrate its application in positron emission tomography (PET) imaging. The in vitro evaluation of 68Ga-DOTA-TAT was assessed in MGC-803 and HT-29 cell lines, and the in vivo evaluation of 68Ga-DOTA-TAT was also performed in mice bearing MGC-803 or HT-29 tumors, respectively. Fluorescence microscopy was also employed to evaluate the specificity of RHO-TAT in vitro in MGC-803 and HT-29 cells as well as ex vivo in tumor slices of the corresponding tumor models. The in vivo imaging differences between 68Ga-DOTA-TAT and 18F-FDG in MGC-803 and HT-29 tumors were also studied. The biodistribution and micro-PET results demonstrated significant uptake of 68Ga-DOTA-TAT in non-FDG-avid MGC-803 tumors, whereas there was negligible uptake in FDG-avid HT-29 tumors. RHO-TAT showed superior fluorescence microscopy imaging effects in MGC-803 cells and tumor slices but not in HT-29 cells and tumor slices, which were consistent with the in vivo results. 68Ga-DOTA-TAT combined with 18F-FDG can be applied noninvasively in cancers with PET imaging for potential patient selection and stratification. We demonstrated a higher binding of 68Ga-DOTA-TAT and RHO-TAT to MGC-803 cells as well as to non-FDG-avid MGC-803 xenografted tumors and a lower binding to HT-29 cells and FDG-avid xenografted tumors. These results suggest that TAT has the potential to be a ligand for targeting certain tumors.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1088-1097"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Easy Access to Bioorthogonal Click-to-Release Reagent Bishydroxy-trans-cyclooctene (C₂TCO) and Harnessing of Its Rapid Labeling and Dissecting Feature in Multicycle Imaging. 生物正交点击释放试剂比羟基反式环烯（C2TCO）的便捷获取及其在多周期成像中的快速标记和解剖特性的利用。

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-04-29 DOI: 10.1021/acs.bioconjchem.4c00495

V Arun, Minju Lee, Hongseo Choi, Sangwoo Lee, Junwon Choi, Tae Hyeon Yoo, Wook Kim, Eunha Kim

{"title":"Easy Access to Bioorthogonal Click-to-Release Reagent Bishydroxy-trans-cyclooctene (C2TCO) and Harnessing of Its Rapid Labeling and Dissecting Feature in Multicycle Imaging.","authors":"V Arun, Minju Lee, Hongseo Choi, Sangwoo Lee, Junwon Choi, Tae Hyeon Yoo, Wook Kim, Eunha Kim","doi":"10.1021/acs.bioconjchem.4c00495","DOIUrl":"10.1021/acs.bioconjchem.4c00495","url":null,"abstract":"Bifunctional trans-cyclooctene (bTCO) with a carbamate or carbonate at the allylic position and tetrazine provide a promising bioorthogonal click chemistry pair for the click-to-release approach, successfully employed in various biotechnological applications. Herein, we demonstrate a simple and straightforward method to synthesize C2TCO, a symmetrical bTCO derivative with two hydroxyl groups at the allylic positions. The efficiently synthesized C2TCO at first was selectively functionalized with a fluorophore (C2TCO-FL), and the conjugate was labeled onto monoclonal antibodies (Ab-C2TCO-FL). The fluorophore of Ab-C2TCO-FL was easily removed from the antibody through the mild treatment of tetrazine, enabling multicycle fluorescent bioimaging. Next, an antibody-drug conjugate targeting PD-L1 was prepared using the linker based on C2TCO. The cytotoxic payload was efficiently released from the antibody upon tetrazine treatment, which induced cellular cytotoxicity.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"930-935"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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