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RETRACTION: High-Resolution Imaging of Human Cancer Proteins Using Microprocessor Materials. RETRACTION:使用微处理器材料对人类癌症蛋白质进行高分辨率成像。
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-11-04 DOI: 10.1002/cbic.202400798
{"title":"RETRACTION: High-Resolution Imaging of Human Cancer Proteins Using Microprocessor Materials.","authors":"","doi":"10.1002/cbic.202400798","DOIUrl":"https://doi.org/10.1002/cbic.202400798","url":null,"abstract":"<p><strong>Retraction: </strong>M. J. Solares, G. M. Jonaid, W. Y. Luqiu, S. Berry, J. Khadela, Y. Liang, M. C. Evans, K. J. Pridham, W. J. Dearnaley, Z. Sheng and D. F. Kelly, \"High-Resolution Imaging of Human Cancer Proteins Using Microprocessor Materials,\" ChemBioChem, 23, no. 17 (2022), e202200310, https://doi.org/10.1002/cbic.202200310. The above article, published online on 5 July 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Ruben Ragg; and Wiley-VCH GmbH. The retraction has been agreed following a thorough peer review process conducted by the author's institution, Penn State. The editors' own independent investigation confirmed that density map for the p53 dimer does not align well with the model for Figures 2B and S3 A. Furthermore, it was found that the coordinate and map files associated with the article available in the Protein Data Bank [PDB accession codes 8F2I (p53 monomer), 8F2H (p53 dimer)] and Electron Microscopy Data Bank [EMDB accession codes EMD28817 (p53 monomer), EMD28816 (p53 dimer)] exhibit poor alignment throughout. In addition, the authors did not provide original research data, maps and models in question, to justify the findings. The editors' own independent investigation confirmed that the conclusions of this manuscript are not sufficiently supported. Author D. F. Kelly responded to our notice of retraction, but did not state their agreement nor disagreement. Author G. M. Jonaid agrees with the retraction. All other authors did not respond to our notice regarding the retraction.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400798"},"PeriodicalIF":2.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574927","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
Chemoenzymatic Cyclization by Vanadium Chloroperoxidase for Synthesis of 4-Hydroxyisochroman-1-Ones. 利用氯过氧化钒酶的化学合成环化作用合成 4-羟基异苯并二氢吡喃-1-酮。
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-11-03 DOI: 10.1002/cbic.202400697
Chisanu Krongyut, Nittaya Wiriya, Worakrit Saiyasombat, Kantapat Chansaenpak, Sineenat Sripattanakul, Anyanee Kamkaew, Rung-Yi Lai
{"title":"Chemoenzymatic Cyclization by Vanadium Chloroperoxidase for Synthesis of 4-Hydroxyisochroman-1-Ones.","authors":"Chisanu Krongyut, Nittaya Wiriya, Worakrit Saiyasombat, Kantapat Chansaenpak, Sineenat Sripattanakul, Anyanee Kamkaew, Rung-Yi Lai","doi":"10.1002/cbic.202400697","DOIUrl":"10.1002/cbic.202400697","url":null,"abstract":"<p><p>4-Hydroxyisochroman-1-ones belong to the class of the secondary metabolite 3,4-dihydroisocoumarins. They exhibit a wide range of biological activities. These compounds can be synthesized through halocyclization using hypervalent iodine species or N-bromosuccinimide, followed by hydrolysis. Nonetheless, the reactions required specific conditions and generated toxic byproducts. In this study, Curvularia inaequalis vanadium chloroperoxidase (CiVCPO) catalyzed the chemoenzymatic cyclization of 2-vinylbenzoic acids with different electron-donating groups (1 a-1 e) to produce good yields of 4-hydroxyisochroman-1-ones (3 a-3 e) by adding KBr and H<sub>2</sub>O<sub>2</sub> in citrate buffer (pH 5). The reaction mixture contained 30 % DMSO to improve substrate solubility without enzyme activity loss. The condition is more environmentally friendly than chemical methods. Therefore, it offers an alternative approach for synthesizing 4-hydroxyisochroman-1-ones.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400697"},"PeriodicalIF":2.6,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566754","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
Distinct Effects of SARS-CoV-2 Protein Segments on Structural Stability, Amyloidogenic Potential, and α-Synuclein Aggregation. SARS-CoV-2 蛋白段对结构稳定性、淀粉样蛋白生成潜能和 α-突触核蛋白聚集的不同影响
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-10-31 DOI: 10.1002/cbic.202400598
Vince St Dollente Mesias, Jianing Zhang, Hongni Zhu, Xin Dai, Jixi Li, Jinqing Huang
{"title":"Distinct Effects of SARS-CoV-2 Protein Segments on Structural Stability, Amyloidogenic Potential, and α-Synuclein Aggregation.","authors":"Vince St Dollente Mesias, Jianing Zhang, Hongni Zhu, Xin Dai, Jixi Li, Jinqing Huang","doi":"10.1002/cbic.202400598","DOIUrl":"10.1002/cbic.202400598","url":null,"abstract":"<p><p>Amyloidosis is characterized by the abnormal accumulation of misfolded proteins, called amyloid fibrils, leading to diverse clinical manifestations. Recent studies on the amyloidogenesis of SARS-CoV-2 protein segments have raised concerns on their potential link to post-infection neurodegeneration, however, the mechanisms remain unclear. Herein, we investigated the structure, stability, and amyloidogenic propensity of a nine-residue segment (SK9) of the SARS-CoV-2 envelope protein and their impact on neuronal protein α-synuclein (αSyn) aggregation. Specifically, the amino acid sequence of the SK9 wildtype has been modified from a basic and positively charged peptide (SFYVYSRVK), to a nearly neutral and more hydrophobic peptide (SAAVASAVK, labelled as SK9 var1), and to an acidic and negatively charged peptide (SDAVANAVK, labelled as SK9 var2). Our findings reveal that the SK9 wildtype exhibited a pronounced amyloidogenic propensity due to its disordered and unstable nature, while the SK9 variants possessed more ordered and stable structures preventing the amyloid formation. Significantly, the SK9 wildtype demonstrated distinct effect on αSyn aggregation kinetics and aggregate morphology to facilitate the formation of αSyn aggregates with enhanced resistance against enzymatic degradation. This study highlights the potential of modifying short peptide sequences to fine-tune their properties, providing insights into understanding and regulating viral-induced amyloid aggregations.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400598"},"PeriodicalIF":2.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556509","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
A Rapid and Sensitive MicroPlate Assay (MPSA) Using an Alkyne-Modified CMP-Sialic Acid Donor to Evaluate Human Sialyltransferase Specificity. 使用炔基修饰的 CMP-唾液酸供体评估人类唾液基转移酶特异性的快速灵敏微板测定 (MPSA)。
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-10-29 DOI: 10.1002/cbic.202400539
Kiamungongo Clairene Filipe, Sushmaa Dangudubiyyam, Cédric Lion, Mathieu Decloquement, Roxana Elin Teppa, Christophe Biot, Anne Harduin-Lepers
{"title":"A Rapid and Sensitive MicroPlate Assay (MPSA) Using an Alkyne-Modified CMP-Sialic Acid Donor to Evaluate Human Sialyltransferase Specificity.","authors":"Kiamungongo Clairene Filipe, Sushmaa Dangudubiyyam, Cédric Lion, Mathieu Decloquement, Roxana Elin Teppa, Christophe Biot, Anne Harduin-Lepers","doi":"10.1002/cbic.202400539","DOIUrl":"10.1002/cbic.202400539","url":null,"abstract":"<p><p>Human sialyltransferases primarily utilize CMP-Sias, especially transferring Neu5Ac from CMP-Neu5Ac to various acceptors. Advances in chemical biology have led to the synthesis of novel CMP-Sia donors suitable for bioorthogonal reactions in cell-based assays. However, the compatibility of these donors with all human enzymes remains uncertain. We synthesized a non-natural CMP-Sia donor with an alkyne modification on the N-acyl group of Neu5Ac, which was effectively used by human ST6Gal I and ST3Gal I. A sensitive MicroPlate Sialyltransferase Assay (MPSA) was developed and expanded to a panel of 13 human STs acting on glycoproteins. All assayed enzymes tolerated CMP-SiaNAl, allowing for the determination of kinetic parameters and turnover numbers. This study enhances the biochemical characterization of human sialyltransferases and opens new avenues for developing sialyltransferase inhibitors.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400539"},"PeriodicalIF":2.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520486","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
Marker-Dependent Cleavage of RNA by Binary (split) DNAzyme (BiDz) and Binary DNA Machines (BiDM). 二元(分裂)DNA 酶(BiDz)和二元 DNA 机(biDNM)对 RNA 的标记依赖性裂解。
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-10-29 DOI: 10.1002/cbic.202400665
Mikhail V Dubovichenko, Daria D Nedorezova, Christina Patra, Valeria S Drozd, Vladimir S Andrianov, Anna I Ashmarova, Vivian O Nnanyereugo, Ahmed A Eldeeb, Dmitry M Kolpashchikov
{"title":"Marker-Dependent Cleavage of RNA by Binary (split) DNAzyme (BiDz) and Binary DNA Machines (BiDM).","authors":"Mikhail V Dubovichenko, Daria D Nedorezova, Christina Patra, Valeria S Drozd, Vladimir S Andrianov, Anna I Ashmarova, Vivian O Nnanyereugo, Ahmed A Eldeeb, Dmitry M Kolpashchikov","doi":"10.1002/cbic.202400665","DOIUrl":"10.1002/cbic.202400665","url":null,"abstract":"<p><p>Oligonucleotide gene therapy (OGT) can be used to suppress specific RNA in cells and thus has been explored for gene therapy. Despite extensive effort, there is no clinically significant OGT for treating cancer. Low efficiency of OGT is one of the problems. Earlier, we proposed to address this problem by suppressing the most vital genes in cancer cells e. g. housekeeping genes. To achieve specific activation of the OGT agents in cancer but not in normal cells, we designed a binary (split) DNAzyme (BiDz) activated by cancer-related nucleic acid sequences. This work is devoted to BiDz optimization for efficient cleavage of structured RNA targets upon activation with a cancer marker-related sequence. To achieve efficient binding of folded RNA, the BiDz was equipped with RNA binding/unwinding arms to produce 'Binary DNA-nanomachines' (BiDM). It was demonstrated that BiDM can improve both the rate and selectivity of RNA cleavage in comparison with BiDz. For the best selectivity, single-nucleotide variations should be recognized by the strand detached from the common DNA scaffold of BiDM. Further development of DNA nanotechnology-inspired agents can advance OGT in treating cancer, viral infections, and genetic disorders.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400665"},"PeriodicalIF":2.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542330","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
A Universal Support for the Solid-Phase Synthesis of Peptidyl-tRNA Mimics. 肽基-tRNA 模拟物固相合成的通用支持。
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-10-28 DOI: 10.1002/cbic.202400717
Julia Thaler, Christoph Mitteregger, Laurin Flemmich, Ronald Micura
{"title":"A Universal Support for the Solid-Phase Synthesis of Peptidyl-tRNA Mimics.","authors":"Julia Thaler, Christoph Mitteregger, Laurin Flemmich, Ronald Micura","doi":"10.1002/cbic.202400717","DOIUrl":"10.1002/cbic.202400717","url":null,"abstract":"<p><p>Hydrolysis-resistant RNA-peptide conjugates that mimic peptidyl-tRNAs are often required for structural and functional studies of protein synthesis at the ribosome. These conjugates can be synthesized by solid-phase chemical synthesis, which allows maximum flexibility in both the peptide and RNA sequence. The commonly used strategy is based on (3'-N-aminoacyl)-3'-amino-3'-deoxyadenosine solid supports, which already contain the first C-terminal amino acid of the target peptidyl chain. This is a limitation in the sense that different individual supports must be synthesized for different C-terminal amino acids. In this study, we demonstrate a solution to this problem by introducing a novel universal support. The key is a free ribose 3'-NH<sub>2</sub> group that can be coupled to any amino acid. This is made possible by a photocleavable ether moiety that links the ribose 2'-O to the support, thus avoiding the typical O-to-N migration that occurs when using 2'-O-acyl linked solid supports. Once assembled, the conjugate is readily cleaved by UV irradiation. The structural integrity of the obtained peptidyl-RNA conjugates was verified by mass spectrometry analysis. In conclusion, the new photocleavable solid support makes the synthesis of 3'-peptidyl tRNA mimics of different peptidyl chains significantly more efficient compared to the commonly used approaches.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400717"},"PeriodicalIF":2.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520487","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
Rewiring Lysine Catabolism in Cancer Leads to Increased Histone Crotonylation and Immune Escape. 癌症中赖氨酸分解代谢的重构导致组蛋白质粒化和免疫逃逸的增加
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-10-27 DOI: 10.1002/cbic.202400638
Kosta Besermenji, Rita Petracca
{"title":"Rewiring Lysine Catabolism in Cancer Leads to Increased Histone Crotonylation and Immune Escape.","authors":"Kosta Besermenji, Rita Petracca","doi":"10.1002/cbic.202400638","DOIUrl":"https://doi.org/10.1002/cbic.202400638","url":null,"abstract":"<p><p>Crotonyl-CoA (cr-CoA) is a metabolite derived directly from the catabolism of lysine (Lys) and tryptophan (Trp) or from the β-oxidation of fatty acids. In glioblastoma stem cells (GSCs), histone H4 crotonylation levels are significantly elevated, which appears to positively correlate with tumor growth. This increase in crotonyl-CoA production is attributed to the overexpression of specific Lys transporters on the cell membrane, leading to higher free lysine levels. Additionally, the overexpression of glutaryl-CoA dehydrogenase (GCDH), the enzyme responsible for crotonyl-CoA production, further contributes to this increase. When GCDH is depleted or under a lysine-restricted diet, genes involved in type I interferon (IFN) signaling are upregulated, resulting in tumor growth suppression. Type I interferons are a group of cytokines critical for antiviral responses and immunoregulation. This highlights how cancer cells exploit crotonylation to modulate the immune response. This work opens up new avenues for investigating how cancer cells rewire their metabolism to increase crotonylation and evade the immune system.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400638"},"PeriodicalIF":2.6,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491547","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
Supramolecular Conductive Hydrogels for Tissue Engineering Applications. 用于组织工程应用的超分子导电水凝胶。
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-10-27 DOI: 10.1002/cbic.202400733
Aashwini Bhavsar, Falguni Pati, Priyadarshi Chakraborty
{"title":"Supramolecular Conductive Hydrogels for Tissue Engineering Applications.","authors":"Aashwini Bhavsar, Falguni Pati, Priyadarshi Chakraborty","doi":"10.1002/cbic.202400733","DOIUrl":"10.1002/cbic.202400733","url":null,"abstract":"<p><p>Owing to their unique attributes, including reversibility, specificity, directionality, and tunability, supramolecular biomaterials have evolved as an excellent alternative to conventional biomaterials like polymers, ceramics, and metals. Supramolecular hydrogels, in particular, have garnered significant interest because their fibrous architecture, high water content, and interconnected 3D network resemble the extracellular matrix to some extent. Consequently, supramolecular hydrogels have been used to develop biomaterials for tissue engineering. Supramolecular conductive hydrogels combine the advantages of supramolecular soft materials with the electrical properties of metals, making them highly relevant for electrogenic tissue engineering. Given the versatile applications of these hydrogels, it is essential to periodically review high-quality research in this area. In this review, we focus on recent advances in supramolecular conductive hydrogels, particularly their applications in tissue engineering. We discuss the conductive components of these hydrogels and highlight notable reports on their use in cardiac, skin, and neural tissue engineering. Additionally, we outline potential future developments in this field.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400733"},"PeriodicalIF":2.6,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491548","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
Cracking Lysine Crotonylation (Kcr): Enlightening a Promising Post-Translational Modification. 破解赖氨酸巴豆酰化(Kcr):揭示一种前景广阔的翻译后修饰。
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-10-27 DOI: 10.1002/cbic.202400639
Marinda Westerveld, Kosta Besermenji, David Aidukas, Nikita Ostrovitsa, Rita Petracca
{"title":"Cracking Lysine Crotonylation (Kcr): Enlightening a Promising Post-Translational Modification.","authors":"Marinda Westerveld, Kosta Besermenji, David Aidukas, Nikita Ostrovitsa, Rita Petracca","doi":"10.1002/cbic.202400639","DOIUrl":"https://doi.org/10.1002/cbic.202400639","url":null,"abstract":"<p><p>Lysine crotonylation (Kcr) is a recently discovered post-translational modification (PTM). Both histone and non-histone Kcr-proteins have been associated with numerous diseases including cancer, acute kidney injury, HIV latency, and cardiovascular disease. Histone Kcr enhances gene expression to a larger extend than the extensively studied lysine acetylation (Kac), suggesting Kcr as a novel potential therapeutic target. Although numerous scientific reports on crotonylation were published in the last years, relevant knowledge gaps concerning this PTM and its regulation still remain. To date, only few selective Kcr-interacting proteins have been identified and selective methods for the enrichment of Kcr-proteins in chemical proteomics analysis are still lacking. The development of new techniques to study this underexplored PTM could then clarify its function in health and disease and hopefully accelerate the development of new therapeutics for Kcr-related disease. Herein we briefly review what is known about the regulation mechanisms of Kcr and the current methods used to identify Kcr-proteins and their interacting partners. This report aims to highlight the significant potential of Kcr as a therapeutic target and to identify the existing scientific gaps that new research must address.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400639"},"PeriodicalIF":2.6,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491540","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
Evaluation of Potency and Specificity of Cryptophycin-Loaded Antibody-Drug Conjugates. 评估隐球菌素负载抗体-药物共轭物的效力和特异性
IF 2.6 4区 生物学
ChemBioChem Pub Date : 2024-10-27 DOI: 10.1002/cbic.202400738
Peter Bitsch, Cedric Dessin, Sebastian Bitsch, Jona Voss, Janine Becker, Panna Sharma, Neha Biyani, Harry Kochat, Norbert Sewald, Harald Kolmar
{"title":"Evaluation of Potency and Specificity of Cryptophycin-Loaded Antibody-Drug Conjugates.","authors":"Peter Bitsch, Cedric Dessin, Sebastian Bitsch, Jona Voss, Janine Becker, Panna Sharma, Neha Biyani, Harry Kochat, Norbert Sewald, Harald Kolmar","doi":"10.1002/cbic.202400738","DOIUrl":"10.1002/cbic.202400738","url":null,"abstract":"<p><p>An enhanced variant of the antimitotic toxin cryptophycin was conjugated to the anti-Her2 monoclonal antibody (mAb) Trastuzumab upon Michael addition. Either antibodies with freed hinge-region cysteines or THIOMAB formats with engineered cysteines in the mAbs light chain were added to a maleimide derivative of cryptophycin. These Antibody-Drug Conjugates (ADCs) showed retained binding to Her2 positive tumor cells and highly efficient cell killing in double-digit pM range on high Her2-expressing SK-BR-3 cells. Two ADCs (DAR 6, DAR 3) showed superior cell killing of the cell lines JIMT-1 and RT112 with medium receptor expression level in comparison with a DAR 6 MMAE ADC serving as reference. The observed cell cytotoxicity is target-dependent since no impact on cell viability was observed for low Her2-expressing MDA-MB468 cells. Particularly the DAR 3 ADC in THIOMAB format exhibiting desirable biophysical properties and high potency emerged as a promising candidate for further in vivo investigations.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400738"},"PeriodicalIF":2.6,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491542","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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