IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-13 DOI: 10.1002/cbic.202500584

Jaspreet Bhamra, Mahati Krishna, George Samaan, Sankha Pattanayak, Swagatam Mukhopadhyay

{"title":"Toxicity of Antisense Oligonucleotides is Determined by the Synergistic Interplay of Chemical Modifications and Nucleotide Sequences, Not by Either Factor Alone.","authors":"Jaspreet Bhamra, Mahati Krishna, George Samaan, Sankha Pattanayak, Swagatam Mukhopadhyay","doi":"10.1002/cbic.202500584","DOIUrl":"https://doi.org/10.1002/cbic.202500584","url":null,"abstract":"Antisense oligonucleotides (ASOs) offer a promising therapeutic approach for precise RNA-level gene modulation. Despite advancements in chemical modifications to enhance stability and pharmacokinetics, ASOs still face significant challenges, including liver, immunological, renal, and neurological toxicities, potentially leading to high preclinical failure rates. Current oligonucleotide-based drug optimization strategies to overcome such issues often rely on applying a few commonly used chemical architectures (patterns of linker, sugar, or base modifications), which are conventional in the field, or engaging in expensive and time-consuming trial-and-error screening processes involving both sequence changes and positional chemical modifications. These traditional approaches treat nucleotide sequences (\"sequence\") and sugar/linkage modification chemistries (\"chemistry\") as independent contributors to toxicity. However, ample evidence in the literature shows that even minor changes in either sequence or chemical modifications can drastically impact toxicity, suggesting an inseparable synergistic relationship between sequence and chemistry. In support of this sequence-chemistry collusion thesis, this manuscript presents a survey of the systemic toxicity potential of several chemically modified gapmer ASOs by investigating the impact of modifying sugar and backbone chemistries on ASO-induced hepatotoxicity, nephrotoxicity, and immune/inflammatory responses. The data unequivocally demonstrate that ASO toxicity is strongly influenced by the interplay between nucleotide sequence, chemical modifications, and the specific position context of those modifications, highlighting the critical need to rationally engineer the optimal sequence and chemical composition to develop safe and active ASO drug candidates instead of discovering suboptimal ASOs through trial-and-error screening campaigns.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500584"},"PeriodicalIF":2.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278573","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

Improving the Gastric Resilience of Ferritin Nanocages by Fabrication with Gelatin for the Development of Oral Iron Supplements. 明胶制备铁蛋白纳米笼提高胃恢复力用于口服补铁剂的研制。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-13 DOI: 10.1002/cbic.202500620

Rohit Kumar Raut, Gargee Bhattacharyya, Swagatika Mallik, Rabindra K Behera

{"title":"Improving the Gastric Resilience of Ferritin Nanocages by Fabrication with Gelatin for the Development of Oral Iron Supplements.","authors":"Rohit Kumar Raut, Gargee Bhattacharyya, Swagatika Mallik, Rabindra K Behera","doi":"10.1002/cbic.202500620","DOIUrl":"https://doi.org/10.1002/cbic.202500620","url":null,"abstract":"Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world, particularly affecting children and women. The first-line treatment for IDA is oral iron supplementation, preferred for its cost-effectiveness and convenience of administration but is often accompanied by side effects like oxidative stress, infections, and low-solubility/precipitation. This study explores the use of ferritins-self-assembled nanocage proteins serving as soluble cellular-iron reservoirs-as a safer alternative for oral iron intervention. Ideal oral iron supplements must withstand gastric conditions, not trigger oxidative stress, and reach the absorption site intact. DNA protection assays and microbial growth studies demonstrate the antioxidative properties of ferritin, contrary to ferrous salts, underscoring its potential as a safer iron supplement. While ferritin shows commendable gastric tolerance, prolonged exposure can hamper its structural integrity/mineral retention. To further enhance its stability, ferritin is fabricated with gelatins, which preserved its structure/iron content under simulated gastric conditions. The combination of inherent antioxidant and controlled iron release properties of ferritin with gelatin's protective effect could help overcome the limitations of the commercial supplements. The findings of this study could pave the way for the development of \"gelatin-coated iron-loaded ferritin\"-based oral formulations as a safer option for IDA management.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500620"},"PeriodicalIF":2.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278600","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

Gold-Mediated Base Pairs in Nucleic Acids: Selective Coordination to Natural and Thiocarbonyl-Modified Cytosines Dependent upon the Oxidation State of Gold. 核酸中金介导的碱基对：与天然和硫羰基修饰的胞嘧啶的选择性配位依赖于金的氧化态。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-13 DOI: 10.1002/cbic.202500565

Kai Kosugi, Ayano Sugawara, Erika Iwase, HeeJu Park, Shoji Fujiwara, Hiroki Kanazawa, Akira Ono, Jiro Kondo

{"title":"Gold-Mediated Base Pairs in Nucleic Acids: Selective Coordination to Natural and Thiocarbonyl-Modified Cytosines Dependent upon the Oxidation State of Gold.","authors":"Kai Kosugi, Ayano Sugawara, Erika Iwase, HeeJu Park, Shoji Fujiwara, Hiroki Kanazawa, Akira Ono, Jiro Kondo","doi":"10.1002/cbic.202500565","DOIUrl":"https://doi.org/10.1002/cbic.202500565","url":null,"abstract":"Gold-mediated base pairing in nucleic acids has remained poorly understood, despite structural analogies with mercury and silver ions known to coordinate selectively to mismatched base pairs. Here, the crystal structures of a CAu(I)C base pair and a CGAu(I)C base triple formed with natural nucleobases are reported. Although solution-phase thermodynamic analysis of Au(I) coordination is technically unfeasible, structural evidence supports its selective insertion into the base mismatches. In contrast, duplexes incorporating 2-thiocytosine form square-planar complexes with Au(III), and melting temperature analysis shows significant thermal stabilization. The distinct coordination geometries of Au(I) and Au(III) arise from differences in oxidation state and preferred coordination numbers, with Au(I) favoring linear two-coordinate structures and Au(III) forming square-planar complexes stabilized by thiocarbonyl donors. These findings establish a structure-guided strategy for oxidation-state-selective metal coordination in nucleic acids, paving the way for the design of metal-responsive DNA architectures with tunable properties.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500565"},"PeriodicalIF":2.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278563","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

Structural and Spectroscopic Insights into Catalytic Intermediates of a [NiFe]-hydrogenase from Group 3. [NiFe]-氢化酶催化中间体的结构和光谱研究

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-13 DOI: 10.1002/cbic.202500692

Marion Jespersen, Christian Lorent, Olivier N Lemaire, Ingo Zebger, Tristan Wagner

引用次数: 0

Interactions of Neurodegenerative Disease Positron Emission Tomography Imaging Probe Candidates with the C-Terminus of α-Synuclein Fibrils. 神经退行性疾病正电子发射断层成像探针候选物与α-突触核蛋白原纤维c端的相互作用。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-13 DOI: 10.1002/cbic.202500578

Kyle D Shaffer, Ryann M Perez, Marshall G Lougee, Vinayak V Pagar, Hee Jong Kim, Ho Young Kim, Benjamin A Garcia, Robert H Mach, E James Petersson

引用次数: 0

C-6-Modified 2-F-Fucose Derivatives as Inhibitors of Fucosyltransferases. c -6修饰的2-F-聚焦衍生物作为聚焦转移酶的抑制剂。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-13 DOI: 10.1002/cbic.202500624

Yanyan Liu, Geert-Jan Boons

{"title":"C-6-Modified 2-F-Fucose Derivatives as Inhibitors of Fucosyltransferases.","authors":"Yanyan Liu, Geert-Jan Boons","doi":"10.1002/cbic.202500624","DOIUrl":"https://doi.org/10.1002/cbic.202500624","url":null,"abstract":"Fluorinated analogs of guanosine-diphosphate-β-L-fucose (GDP-Fuc) have received considerable attention for the development of inhibitors of fucosyltransferases (FUTs). These compounds can be recognized by FUTs but do not transfer or transfer slowly the fluorinated fucosyl residue because the electron-withdrawing fluorine(s) destabilize the oxocarbenium-like transition state. Fluorinated GDP-Fuc analogs can also act as feedback inhibitor of the de novo biosynthetic pathway of GDP-Fuc. To investigate the biological significance of distinct glycoconjugate classes, it is important to develop inhibitors that can selectively target specific FUT enzymes. The design, synthesis, and biological evaluation of a series of GDP-2-F-Fuc analogs modified at C-6 of Fuc by various amides and ethers are reported. Corresponding prodrugs are also prepared and examined as potential FUT inhibitors of cellular glycosylation. The findings reveal that two of the inhibitors potently inhibited FUT1, 3, 6, and 9, while displaying minimal activity against FUT8. However, the corresponding prodrugs do not inhibit cellular fucosylation, which is probably due to a lack of GDP-fucose pyrophosphorylase activity. The results demonstrate that modifications at the C-6 position of Fuc can confer selectivity, although further investigations of alternative functional groups are required to enhance cellular tolerance and efficacy.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500624"},"PeriodicalIF":2.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278480","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

Citrus Flavonoids for Cystic Fibrosis Treatment. 柑橘类黄酮治疗囊性纤维化。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-10 DOI: 10.1002/cbic.202500586

Mario Pagliaro, Caterina Di Sano, Claudia D'Anna, Giovanna Li Petri, Giuseppe Angellotti, Rosaria Ciriminna

引用次数: 0

Rieske Oxygenase-Catalyzed Biotransformations in Recombinant Cupriavidus necator Fueled by Formate Oxidation. 甲酸氧化催化Rieske加氧酶催化重组铜藻反应器的生物转化。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-09 DOI: 10.1002/cbic.202500722

Marleen Hallamaa, Hannah Pia Franziska Meier, Matteo Vajente, Mattia Ghirardi, Jan Deska, Sandy Schmidt

{"title":"Rieske Oxygenase-Catalyzed Biotransformations in Recombinant Cupriavidus necator Fueled by Formate Oxidation.","authors":"Marleen Hallamaa, Hannah Pia Franziska Meier, Matteo Vajente, Mattia Ghirardi, Jan Deska, Sandy Schmidt","doi":"10.1002/cbic.202500722","DOIUrl":"https://doi.org/10.1002/cbic.202500722","url":null,"abstract":"The use of single carbon (C1) molecules, such as carbon dioxide or formate, is crucial in the transition from a linear, petroleum-based economy to a circular bioeconomy. Formate can serve as both a carbon and energy source, further enhancing its attractiveness as a feedstock. Cupriavidus necator, a lithoautotrophic microbial chassis strain, provides an opportunity to leverage formate for the synthesis of valuable products. However, its ability to grow on formate and the subsequent coupling of that process to recombinantly produced redox enzymes for the efficient production of high-value-added products in a biotransformation has not yet been established. Here, we report the development of a formate-driven C. necator whole-cell chassis that recombinantly produces Rieske oxygenases (ROs) and elaborate on possible stress responses of the cells during formatotrophic cultivation. The whole-cell chassis efficiently catalyzes the oxyfunctionalization of olefins fueled by formate oxidation. For instance, styrene is dihydroxylated to (R)-1-phenylethane-1,2-diol in an excellent 95% yield and with good enantioselectivity (74% ee) under formatotrophic conditions. The product yield and optical purity obtained demonstrate the synthetic usefulness of formate-fueled whole-cell bio-transformations in C. necator.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500722"},"PeriodicalIF":2.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249078","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

Model-Based Optimization of Fed-Batch In Vitro Transcription. 饲料批量体外转录的模型优化

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-09 DOI: 10.1002/cbic.202500485

Nathan Merica Stover, Soroush Ahmadi, Jacob Rosenfeld, Francesco Destro, Allan S Myerson, Richard D Braatz

{"title":"Model-Based Optimization of Fed-Batch In Vitro Transcription.","authors":"Nathan Merica Stover, Soroush Ahmadi, Jacob Rosenfeld, Francesco Destro, Allan S Myerson, Richard D Braatz","doi":"10.1002/cbic.202500485","DOIUrl":"https://doi.org/10.1002/cbic.202500485","url":null,"abstract":"Recent developments in RNA vaccines and therapeutics have motivated the need for process engineering strategies to optimize the in vitro transcription (IVT) reaction for RNA synthesis. Specifically, practitioners seek to maximize the production of RNA and the incorporation of the 5-prime cap to the end of each RNA molecule while minimizing the use of expensive reagents. Fed-batch IVT is a promising technique for achieving these goals but is difficult to optimize by purely experimental means. Herein, a mechanistic model for fed-batch IVT is developed and it is used to develop optimized fed-batch protocols to maximize the formation of RNA while controlling concentrations of nucleoside triphosphates. On a model sequence that has been shown to be sensitive to salt concentrations, this approach can produce twice as much RNA as a heuristic approach. In addition, it is observed and characterized for the first time the formation of magnesium phosphate crystals during the IVT reaction. Strategies informed by thermodynamic modeling are developed to prevent this undesired crystallization during fed-batch IVT. Finally, co-transcriptional capping is incorporated into the model-based optimization approach and a strategy to maximize RNA formation is developed while maintaining a high level of 5-prime cap incorporation and minimizing the use of cap analogs.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500485"},"PeriodicalIF":2.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249008","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

Ratiometric Detection of pH-Induced i-Motif Folding Based on a Dual Emissive Cytosine Analog. 基于双发射胞嘧啶类似物的ph诱导i基序折叠的比率检测。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2025-10-08 DOI: 10.1002/cbic.202500526

Nicolas P F Barthes, Hoang-Ngoan Le, Benoît Y Michel, Alain Burger

{"title":"Ratiometric Detection of pH-Induced i-Motif Folding Based on a Dual Emissive Cytosine Analog.","authors":"Nicolas P F Barthes, Hoang-Ngoan Le, Benoît Y Michel, Alain Burger","doi":"10.1002/cbic.202500526","DOIUrl":"https://doi.org/10.1002/cbic.202500526","url":null,"abstract":"A dual-emissive cytosine analog (TCC), based on a 2-thienyl-3-hydroxychromone scaffold, is incorporated into oligodeoxynucleotides to monitor the folding state of DNA i-motif structures. This modified nucleobase exhibits two distinct emission bands (IN* and IT*), each responding differently to microenvironmental changes, enabling ratiometric detection. The photophysical properties of TCC are systematically characterized in various solvents and DNA contexts, including single-stranded, double-stranded, and i-motif-forming sequences. The IN*/IT* emission ratio and the wavelength of the IT* band act as robust and orthogonal reporters of hydration, base stacking, and protonation states. In fully paired duplexes, the T* band is quenched and blue-shifted, while i-motif folding results in both fluorescence enhancement and a redshift of the T* emission. Additionally, the probe distinguishes mismatched base pairs and abasic sites, offering further insights into local structural defects. Overall, this ratiometric nucleobase analog enables real-time, multiparametric monitoring of i-motif folding with high sensitivity, and holds promise for extension to other noncanonical DNA structures. The findings further establish the 3-hydroxychromone platform as a powerful tool for the rational design of fluorescent sensors targeting dynamic nucleic acid architectures.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500526"},"PeriodicalIF":2.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243332","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

ChemBioChem最新文献