{"title":"Small Molecule Fluorescent Probes for Glutathione S-Transferase.","authors":"Pingping Lu, Huiting Huang, Jia Liu, Yixuan Cao, Sheng Hua Liu, Jun Yin","doi":"10.1002/cbic.202400994","DOIUrl":"10.1002/cbic.202400994","url":null,"abstract":"<p><p>Cytoplasmic glutathione S-transferase (GST) is a key enzyme in cellular detoxification, catalysing the nucleophilic attack of glutathione (GSH) with toxic electrophilic substrates to produce less harmful compounds, thus aiding cellular detoxification. Studies have shown that GST is closely associated with the development of resistance to chemotherapeutic drugs, pesticides, herbicides and antibiotics, and the development of drug resistance in organisms poses new challenges in areas such as environmental protection and tumour therapy. In order to clarify the mechanism of GST in the development of drug resistance and detect the content of GST more accurately, this paper summarized the mechanism of GST on the development of drug resistance in different organisms, the types and research progress of organic small molecule fluorescence probes for GST imaging detection are introduced.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400994"},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447799","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}
ChemBioChemPub Date : 2025-02-19DOI: 10.1002/cbic.202400935
Daniel Szames, Dr. Shana O. Kelley
{"title":"Mitochondria-Targeted Temozolomide Probe for Overcoming MGMT-Mediated Resistance in Glioblastoma","authors":"Daniel Szames, Dr. Shana O. Kelley","doi":"10.1002/cbic.202400935","DOIUrl":"10.1002/cbic.202400935","url":null,"abstract":"<p>Temozolomide (Tmz) is a DNA methylating agent used for the treatment of glioblastoma multiforme (GBM). Resistance to Tmz in GBM is caused by the DNA direct repair enzyme O<sup>6</sup>-methylguanine DNA methyltransferase (MGMT), which is expressed in ~50 % of GBM tumours. It has yet to be confirmed that MGMT acts within mitochondria to repair mitochondrial DNA (mtDNA), and in this report we discuss the development of a novel mitochondria-targeted temozolomide probe (mtTmz) for evading MGMT-mediated resistance. Through conjugation of Tmz to a mitochondria-penetrating peptide (MPP), exclusive mitochondrial localization was achieved, and the probe retained alkylation activity demonstrated by chemical and DNA-based assays. Absence of nuclear DNA damage was assessed by detecting γH2AX foci. mtTmz demonstrated efficient cell killing capabilities independent of MGMT status in GBM cells as determined by cell viability assays. It was determined using a Proteinase K digestion assay that MGMT does not translocate to mitochondria in response to mtTmz treatment, and RT-qPCR analysis demonstrated that mtTmz does not induce MGMT gene expression compared to Tmz. The results reported highlight both the potential of mitochondrial targeting of Tmz and mitochondria as a therapeutic target in MGMT-expressing GBM.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202400935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2025-02-19DOI: 10.1002/cbic.202401066
Dr. Yuji Nishiuchi, Dr. Sofia Elouali, Dr. Masato Noguchi, Dr. Hirofumi Ochiai
{"title":"Conjugation of Human N-Glycans Improves the Drug Properties of Existing Peptides and Proteins","authors":"Dr. Yuji Nishiuchi, Dr. Sofia Elouali, Dr. Masato Noguchi, Dr. Hirofumi Ochiai","doi":"10.1002/cbic.202401066","DOIUrl":"10.1002/cbic.202401066","url":null,"abstract":"<p>Glycosylation is one of the most ubiquitous post-translational modifications observed in peptides and proteins. It affects the structural and functional characteristics of these macromolecules, thereby exerting a profound influence on a multitude of biological processes. <i>N</i>-Glycans are expected to be a beneficial modifier for increasing the solubility and <i>in vivo</i> half-life, and reducing the aggregation and immunogenicity of native bioactive peptides and proteins, which have seen limited clinical utility due to their short blood half-life and unsuitable physicochemical properties. Chemoselective glycosylation reactions that can be conducted post-synthesis and in aqueous conditions are a promising strategy for the high-throughput development of peptide/protein drugs. This “glycoconjugation” approach is particularly advantageous in that manipulation of glycan protecting groups is not necessary, thereby allowing conjugation reactions to be carried out between target molecules and unprotected glycans. By providing a single glycosylation profile, i. e., glycan structure, number, and position, glycoconjugation not only allows the beneficial properties of <i>N</i>-glycans to be exploited, but also facilitates the investigation of <i>N</i>-glycan function.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456447","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}
{"title":"Wireframe DNA Origami Capable of Vertex-protruding Transformation.","authors":"Yosuke Ochi, Wataru Kato, Yoichi Tsutsui, Yuki Gomibuchi, Daichi Tominaga, Keisuke Sakai, Takeshi Araki, Suzunosuke Yoshitake, Takuo Yasunaga, Yusuke V Morimoto, Kazuhiro Maeda, Junichi Taira, Yusuke Sato","doi":"10.1002/cbic.202401071","DOIUrl":"10.1002/cbic.202401071","url":null,"abstract":"<p><p>Regulating dynamic behavior of the designed molecular structures provides a foundation for the construction of functional molecular devices. DNA nanotechnology allows conformational changes in two-dimensional and three-dimensional DNA origami nanostructures by introducing flexibility between the faces of the structures. However, dynamic transformations in wireframe DNA origami, composed solely of vertices and edges, remain challenging due to vertex-specific flexibility. We report a wireframe DNA origami capable of vertex-protruding transformation between the open- and closed-form with eight protruding vertices. This reversible transformation is driven by DNA hybridization and a toehold-mediated strand displacement reaction. Spacer strands between vertices and edges were designed to introduce flexibility. Coarse-grained molecular dynamics simulations demonstrated that a longer spacer increases conformational flexibility and can achieve the narrow angles required for the vertex-protruding transformation. The experimental results showed the successful assembly of the open-form structure under optimized salt conditions, as visualized through transmission electron microscopy images. Furthermore, the transformation between the open- and closed-form structures was demonstrated by the sequential addition of signal strands. This vertex-protruding transformation mechanism will expand the design approach of dynamic DNA nanostructures and help develop functional molecular devices for artificial molecular systems.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202401071"},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456450","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}
ChemBioChemPub Date : 2025-02-18DOI: 10.1002/cbic.202580404
Dr. Abdulkadir Yayci, Dr. Yen-Hua Huang, Dr. Peta J. Harvey, Prof. David J. Craik
{"title":"Cover Feature: Recombinant Production of The Cyclotide Kalata B1 by Conditional Split Inteins (ChemBioChem 4/2025)","authors":"Dr. Abdulkadir Yayci, Dr. Yen-Hua Huang, Dr. Peta J. Harvey, Prof. David J. Craik","doi":"10.1002/cbic.202580404","DOIUrl":"https://doi.org/10.1002/cbic.202580404","url":null,"abstract":"<p>This illustration represents the facile scalability and ease of operation of a workflow designed for the mass production of cyclotides from recombinantly expressed split inteins. Conversion of precursor proteins, easily produced and purified from <i>E. coli</i>, proceeds by simply mixing two fragments of a split intein to yield the desired cyclic peptide. More information can be found in the article 10.1002/cbic.202400591 by David J. Craik and co-workers. Cover art designed by Dr Peta J. Harvey.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202580404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2025-02-18DOI: 10.1002/cbic.202580401
Rebecca Freeman, Michael J. Bollong
{"title":"Front Cover: HPPE Activates NRF2 Signaling by Liberating Heavy Metal Stores (ChemBioChem 4/2025)","authors":"Rebecca Freeman, Michael J. Bollong","doi":"10.1002/cbic.202580401","DOIUrl":"https://doi.org/10.1002/cbic.202580401","url":null,"abstract":"<p>Small molecule ionophore, HPPE, is depicted as a magnet, acting to liberate cellular stores of Zn<sup>2+</sup> and Cu<sup>2+</sup>. Increased levels of labile metal pools result in nonlethal of oxidative stress in cells, sensed by NRF2 repressor protein and oxidative stress sensor, KEAP1. Consequently, NRF2 is stabilized, resulting in the transcriptional activation of cytoprotective genes, illustrated as a shield with a medical cross. More details can be found in the article 10.1002/cbic.202400529 by Rebecca Freeman and Michael J. Bollong.<figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202580401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2025-02-18DOI: 10.1002/cbic.202400900
Xin-Xin Peng, Xiang-Yu Tan, Hang Zhang, Song Gao, Jun-Long Zhang
{"title":"Anti-Neoplastic Gallium-Based PROTAC for PDI Degradation Triggers Autophagy and Immunogenic Cell Death","authors":"Xin-Xin Peng, Xiang-Yu Tan, Hang Zhang, Song Gao, Jun-Long Zhang","doi":"10.1002/cbic.202400900","DOIUrl":"10.1002/cbic.202400900","url":null,"abstract":"<p>Protein disulfide isomerase (PDI), a family of thiol-disulfide oxidoreductases, is one of the most abundant soluble proteins in the endoplasmic reticulum (ER) and is responsible for protein folding. Increasing evidence suggests that PDI is overexpressed in multiple types of cancer, positioning it as a promising target for tumor therapy. We have designed and synthesized a series of gallium complex-based proteolysis targeting chimeras (PROTACs), which exhibited effective targeting and degradation of PDI in vitro. After analyzing the relationship between structure and function, we have identified <b>M-2</b> as the compound that most efficiently degrades PDI. Our research shows that <b>M-2</b>-induced degradation of PDI can trigger the unfolded protein response, leading to cell autophagy and initiating immunogenic cell death (ICD), as demonstrated in mouse models. This study suggests a potential opportunity for combining PDI targeting and immunotherapy.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439321","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}
ChemBioChemPub Date : 2025-02-18DOI: 10.1002/cbic.202400973
Lingjun Wan, Zhiyuan Zhu, Mengzhou Wei, Prof. Yulin Li
{"title":"Impact of DNA Nick on the Self-Assembly of Single-Tile-Based Polyhedra","authors":"Lingjun Wan, Zhiyuan Zhu, Mengzhou Wei, Prof. Yulin Li","doi":"10.1002/cbic.202400973","DOIUrl":"10.1002/cbic.202400973","url":null,"abstract":"<p>Tile-based self-assembly is a simple yet highly efficient bottom-up nanofabrication strategy, which has been widely applied in many fields such as structural DNA nanotechnology. The self-assembly of DNA tile is determined by not only the sequence design, but also the existing nick in the tile, as it would influence the flexibility and the symmetry of the tile. Herein, we systematically investigated the impact of nick on the tile-based assembly of three-dimensional (3D) DNA polyhedra in various conditions. A series of tile concentrations, four different sticky ends, two annealing approaches, buffers with different metal cations, and different molar percentages of intact tiles, were all tested. It was found that the tile concentration and the valence of metal cations played significant roles in how DNA nick influenced the assembly of DNA polyhedra. Besides, when the molar percentage of intact tiles was higher than the threshold of about two-thirds, the impact of nick on the assembly of DNA polyhedra would not be obvious. Our work provides an insightful understanding of the role of nick in the fabrication of high-quality structures from single-tile-based assembly.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447796","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}
ChemBioChemPub Date : 2025-02-18DOI: 10.1002/cbic.202580402
Niels Borlinghaus, Donato Calabrese, Lars Lauterbach, Bettina M. Nestl
{"title":"Cover Feature: Synthesis of Substituted Acyclic and Cyclic N-Alkylhydrazines by Enzymatic Reductive Hydrazinations (ChemBioChem 4/2025)","authors":"Niels Borlinghaus, Donato Calabrese, Lars Lauterbach, Bettina M. Nestl","doi":"10.1002/cbic.202580402","DOIUrl":"https://doi.org/10.1002/cbic.202580402","url":null,"abstract":"<p>The imine reductase (IRED) from <i>Myxococcus stipitatus</i> catalyses the reductive amination of structurally diverse carbonyls and dicarbonyls with hydrazines (reductive hydrazination), which are also known as rocket fuels. This efficient process produces acyclic and cyclic <i>N</i>-alkylhydrazines, demonstrating the scalability and potential of IREDs for sustainable ′green′ chemical synthesis using H₂ as the reducing agent. More information can be found in the article 10.1002/cbic.202400700 by Lars Lauterbach, Bettina M. Nestl and co-workers. Illustration by Lutz Kupferschläger.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202580402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2025-02-18DOI: 10.1002/cbic.202400982
Matthias Pretzler, Annette Rompel
{"title":"Beyond Phenolics: Alternative Substrates for Type III Copper Enzymes","authors":"Matthias Pretzler, Annette Rompel","doi":"10.1002/cbic.202400982","DOIUrl":"10.1002/cbic.202400982","url":null,"abstract":"<p>The type III copper enzyme family of tyrosinases (TYRs) catalyzes the <i>ortho</i>-hydroxylation and oxidation of phenols as well as the two-electron oxidation of catechols to <i>ortho</i>-quinones. TYRs use copper ions as their tightly bound cofactors and utilize molecular oxygen as their cosubstrate. They are responsible for physiologically important reactions like the formation of melanin, the primary pigment animals apply for protection against UV light. While the reactivity of TYRs on substrates containing aromatic hydroxy groups (<i>i. e</i>. phenols) is well recognized, reports clearly demonstrating that TYRs are active on aromatic amines as well have gone largely unnoticed. In this perspective we aim to bring together the sparse data on non-phenolic TYR substrates to illustrate the potential of TYRs for the oxidation of aminophenols and anilines. The activity of TYRs on aromatic amines extends the substance classes amenable to biotechnological production with TYRs from catechols to <i>N</i>-phenyl imines and phenoxazinone derivates and calls for the inclusion of TYRs among the candidates for oxidative modification of aromatic amines in metabolic pathways.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 7","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202400982","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}