ChemBioChemPub Date : 2026-04-28DOI: 10.1002/cbic.202500976
Lei Liu, Peiyong Song, Meiqi Luo, Li Zhao, Yiyang Lin
{"title":"Sensing the Light With Artificial Cells.","authors":"Lei Liu, Peiyong Song, Meiqi Luo, Li Zhao, Yiyang Lin","doi":"10.1002/cbic.202500976","DOIUrl":"https://doi.org/10.1002/cbic.202500976","url":null,"abstract":"<p><p>Nature has evolved sophisticated light-harvesting systems and sensory mechanisms that detect light, convert it into biochemical energy, regulate biological processes, and synthesize organic compounds and oxygen. Extensive studies have explored the chemical and physical principles underlying the structure and function of photoreceptors and chromophore-embedded proteins, providing insights into light-matter interactions in biological systems. Artificial cells, designed to replicate natural cells, offer a unique platform for investigating biological processes and the origins of life. The development of hierarchical structures capable of light harvesting, sensory detection, and photoenergy conversion is a critical step toward creating effective cell mimics. This review highlights the role of photosensation and photoenergy transduction in biology, summarizes the bottom-up construction of artificial cells, and examines recent advancements in light-harvesting, phototransduction, and energy conversion within these systems, along with light-controlled cytomimetic behaviors.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e202500976"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758157","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 : 2026-04-28DOI: 10.1002/cbic.70350
Elena Frasnetti, Francesco Frigerio, Fabrizio Cinquini, Stefano A Serapian, Silvia Pavoni, Giorgio Colombo
{"title":"Use of Computational Models to Investigate Human Targets of Small Ubiquitous Molecules.","authors":"Elena Frasnetti, Francesco Frigerio, Fabrizio Cinquini, Stefano A Serapian, Silvia Pavoni, Giorgio Colombo","doi":"10.1002/cbic.70350","DOIUrl":"https://doi.org/10.1002/cbic.70350","url":null,"abstract":"<p><p>The effects on human health of chemical compounds, which might be present in the environment due to natural or anthropogenic causes, are a fundamental aspect to be considered for the protection of public health and workers' health and in the evaluation of industrial processes in terms of health protection and sustainability. Investigations focused on lesser known effects that have recently drawn more attention on potential human target proteins. Due to the complexity of biochemical interactions, it is not straightforward to determine the biological response resulting from exposure to a specific chemical. In this article, we tackle this issue by combining chemoinformatics tools and atomistic modeling to perform target identification for several compounds. The study was carried out using a publicly available database that collects relationships between chemicals, genes, and phenotypes and resulting diseases to validate the results of the target identification pipeline. Small molecules that may occur in occupational and nonoccupational settings were investigated. Finally, we discuss the potentialities and limitations of using these fast, computationally inexpensive methods in early-stage target identification, both with and without performing a literature search for experimental data.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70350"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758160","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 : 2026-04-28DOI: 10.1002/cbic.70360
Takanori Uzawa, Seiichi Tada, Chinmay Phadke, Marziyeh Karimiavargani, Liping Zhu, Gang Huang, Wei Wang, Naoto Nemoto, Yoshihiro Ito
{"title":"Fluorogenic Peptide Aptamer Generated Using Bioorthogonal cDNA Display Technology for Cellular Imaging of Heat Shock Protein 90α.","authors":"Takanori Uzawa, Seiichi Tada, Chinmay Phadke, Marziyeh Karimiavargani, Liping Zhu, Gang Huang, Wei Wang, Naoto Nemoto, Yoshihiro Ito","doi":"10.1002/cbic.70360","DOIUrl":"https://doi.org/10.1002/cbic.70360","url":null,"abstract":"<p><p>Fluorogenic probes are valuable tools for rapid detection and bioimaging of target molecules without requiring bound/free separation. Although antibody-based probes are widely used, their large size, reliance on secondary labeling, and limited accessibility to some intracellular regions can restrict their utility. In contrast, fluorogenic peptide aptamers-compact, chemically synthesizable, and self-reporting-offer a promising alternative. Here, we developed a method to prepare a fluorophore-conjugated peptide library using cDNA display and applied it to the selection of fluorogenic peptides targeting heat shock protein 90α (Hsp90α), a clinically relevant biomarker. As the solvatochromic reporter, we used an environmentally sensitive fluorophore, 4-N, N-dimethylamino-1,8-naphthalimide (4-DMN). One selected peptide, Peptide2, exhibited fluorescence enhancement in the presence of Hsp90α while remaining largely unresponsive to the homologous Hsp70. In fixed cells, Peptide2 produced intracellular fluorescence patterns that partially overlapped with those obtained using an anti-Hsp90α antibody, supporting its ability to detect intracellular Hsp90α-related signals. Peptide2 and the antibody also showed partially distinct staining distributions, suggesting differences in epitope accessibility and/or intracellular accessibility. These results establish a proof of concept for generating target-responsive, self-reporting peptide probes using bioorthogonal cDNA display.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70360"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758053","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 : 2026-04-28DOI: 10.1002/cbic.202500875
Aima Ghouri, Muhammad Atiq Ur Rehman, Rizwan Ahmed Malik, Hussein Alrobei
{"title":"Ficus carica Extract Loaded 3D-Printed Sodium Alginate/Guar Gum Scaffolds for Potential Wound Healing Applications: An In Vitro Study.","authors":"Aima Ghouri, Muhammad Atiq Ur Rehman, Rizwan Ahmed Malik, Hussein Alrobei","doi":"10.1002/cbic.202500875","DOIUrl":"https://doi.org/10.1002/cbic.202500875","url":null,"abstract":"<p><p>Skin burns are a major health concern that is caused by severe electric shocks, chemical and thermal exposure. The intense skin burns can cause the fibroblast cell death which can lead to the delayed wound healing. Direct ink write (DIW) printing is a promising three-dimensional (3D) printing technology that provides availability of different polymeric solutions and incorporation of bioactive agents within the polymeric blends with low material wastage. Herein, we fabricated a promising combination of ink consisting of sodium alginate (Na-ALG), guar gum (GG), and Ficus carica (FC) for DIW printing. The formulated scaffolds showed favorable rheological properties and layer fidelity. The scaffolds depicted appropriate intercrosslinked porous morphology that supported swelling ability. Na-ALG/GG/FC scaffolds were biodegradable, released gallic acid (GA) and demonstrated antibacterial efficacy against Escherichia coli and Staphylococcus aureus. Scaffold exhibited biocompatibility of 109% on Day 7 with fibroblasts and released vascular endothelial growth factor (VEGF) which indicated formation of new blood vessels. Hence, Na-ALG/GG/FC scaffolds are a potential candidate for treating chronic wounds.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e202500875"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758095","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 : 2026-04-28DOI: 10.1002/cbic.70352
Jhilik Mondal, Afzal Azim, Syed Masood Husain
{"title":"Enzyme-Coupled Fluorescence Assays for the Detection and Quantification of Amino Acids.","authors":"Jhilik Mondal, Afzal Azim, Syed Masood Husain","doi":"10.1002/cbic.70352","DOIUrl":"10.1002/cbic.70352","url":null,"abstract":"<p><p>Amino acids are fundamental to cellular physiology, and deviations in their concentrations are closely linked with metabolic and pathological disorders. Accurate and rapid quantification of amino acids is therefore essential for clinical diagnostics and biomedical research. However, conventional enzymatic assays based on absorbance detection typically lack the sensitivity required for clinical amino acid analysis. In this study, we developed enzyme-based assays for the detection and quantification of four clinically relevant amino acids, L-valine, L-phenylalanine, L-proline, and L-lysine, representing branched-chain, aromatic, cyclic, and basic amino acids, respectively. Recombinant dehydrogenases specific to each amino acid were coupled with a resazurin-based fluorescence readout, enabling highly sensitive detection of NADH generated during amino acid oxidation. The assays demonstrated high specificity toward their respective amino acids and enabled quantification in the submillimolar range using minimal sample volumes. Moreover, application to serum samples from sepsis patients revealed accurate amino acid concentrations, which were further validated by NMR spectroscopy, showing a strong correlation (R<sup>2</sup> = 0.97-0.99). The fluorescence-based assay required only 15-20 µL of serum and delivered results within 30-40 min, highlighting its potential for point-of-care diagnostics.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70352"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727803","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 : 2026-04-28DOI: 10.1002/cbic.70342
Vivian P Willers, Nikola Lončar, Marco W Fraaije
{"title":"Biocatalytic Indigo Synthesis From L-Tryptophan Using a Three-Step Cascade Without Cofactor Regeneration.","authors":"Vivian P Willers, Nikola Lončar, Marco W Fraaije","doi":"10.1002/cbic.70342","DOIUrl":"10.1002/cbic.70342","url":null,"abstract":"<p><p>Indigo is currently produced from petrochemical sources, which poses significant environmental challenges. Sustainable biotechnological alternatives are therefore highly desirable. Enzymatic synthesis of indigo from L-tryptophan via indole has been demonstrated, but conventional pathways based on flavin-containing monooxygenases require costly coenzymes such as NAD(P)H, limiting their practical applicability. In this study, we present a novel, self-sufficient, NAD(P)H-independent enzyme cascade for indigo biosynthesis from the renewable feedstock L-tryptophan. The cascade starts with conversion of L-tryptophan into indole and pyruvate by a tryptophanase. As next steps, the system couples an engineered bacterial tyrosine hydroxylase, which converts indole into indoxyl using hydrogen peroxide, with a pyruvate oxidase that generates the required peroxide in situ. The cascade thereby transforms a reaction byproduct into the oxidizing equivalent needed for the subsequent step, establishing a closed catalytic cycle with minimal auxiliary inputs. After optimizing cascade parameters, the system produced 0.25 mM indigo from 5 mM L-tryptophan. Although the overall yield remains moderate, this proof-of-principle demonstrates a sustainable and cost-effective enzymatic route for indigo production from biobased starting materials, providing an environmentally friendly alternative to petrochemical synthesis.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70342"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727846","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 : 2026-04-28DOI: 10.1002/cbic.202500743
Julia Wirmer-Bartoschek, Jan-Peter Ferner, Alexander Heckel, Harald Schwalbe
{"title":"Dissecting the Chemical and Thermal Stabilities of Tetrads in G-Quadruplexes to Derive a Structure-Activity Relation for a Thrombin-Binding DNA G-Quadruplex Aptamer.","authors":"Julia Wirmer-Bartoschek, Jan-Peter Ferner, Alexander Heckel, Harald Schwalbe","doi":"10.1002/cbic.202500743","DOIUrl":"10.1002/cbic.202500743","url":null,"abstract":"<p><p>Guanosine- and deoxyguanosine-rich nucleic acids can form G-quadruplex structures (G4) that are stabilized by guanine tetrads (G4 tetrads). G4s find numerous applications in biotechnology. Here, we study a so called thrombin-binding aptamer (TBA), developed by SELEX procedures, that adopts a G4 conformation and inhibits clotting of thrombin. We investigate the TBA G4 and its variants with either four adenosine desoxynucleotides or four abasic sites attached either to the 5'-terminus (A4-TBA and ab4-TBA) or the 3'-terminus (TBA-ab4 and TBA-A4). These variants have been shown to exhibit differential anticlotting activities previously. The variant TBA-ab4, which was the most biological active in earlier investigations, has an exceptional stability against nuclease restriction, while all other variants show similar decay rates in mammalian serum. Biophysical characterization of the variants reveals that the structure of the aptamer remains unchanged, but that also their different thermal stabilities correlate with the anticlotting activity of TBA. Hydrogen exchange quantified by nuclear magnetic resonance spectroscopy (NMR) reveals individual G4 tetrad thermodynamics. Our data indicate that while enthalpy, entropy and free energy of base pair opening show surprisingly low variation, a hotspot for stabilization of the G4 is present at the 3', 5' terminal tetrad of TBA.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e202500743"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727860","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 : 2026-04-14DOI: 10.1002/cbic.70319
Fredrik Sjövall, Ulf J Nilsson
{"title":"β-Mannosyl Triazoles as Mimics of Galactosyl Galectin-3 and Galectin-9 N-Terminal Domain Inhibitors.","authors":"Fredrik Sjövall, Ulf J Nilsson","doi":"10.1002/cbic.70319","DOIUrl":"10.1002/cbic.70319","url":null,"abstract":"<p><p>Mannosyl β-C-1 amidotriazoles have previously been reported to have higher selectivity for galectin-9N (N-terminal domain) than the corresponding galactoside C3 amidotriazoles have, which were more selective for galectin-3. This study further investigated this by synthesis of mono- and bis-aryltriazolyl mannoside analogues to known high-affinity galectin-3 galactosyl-derived inhibitors. Following synthesis, affinity measurements using competititve fluorescence polarization assays were performed which indicated low affinity of the bis-aryltriazolyl mannosyls, while the mono-aryltriazolyl mannosyls analogs possessed improved affinity, albeit with lower and selectivity. From conformational calculations it was implied that the weak-binding bis-aryltriazolyl mannosyl analogues do not find the same conformation and binding pose as the parent galactoside compounds.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 7","pages":"e70319"},"PeriodicalIF":2.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13072086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669200","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 : 2026-04-14DOI: 10.1002/cbic.202500894
Yongqing Ma, Yifeng Huang, Yuxuan Yan, Hongchao Shi, Yongbin Cui, Junmian Yang, Kuo Ren, Jie Feng
{"title":"Recent Advances in Asymmetric Synthesis of 1,4-Dihydropyridines.","authors":"Yongqing Ma, Yifeng Huang, Yuxuan Yan, Hongchao Shi, Yongbin Cui, Junmian Yang, Kuo Ren, Jie Feng","doi":"10.1002/cbic.202500894","DOIUrl":"https://doi.org/10.1002/cbic.202500894","url":null,"abstract":"<p><p>The 1,4-dihydropyridine (1,4-DHP) scaffold is a privileged scaffold in numerous therapeutic agents, including L-type calcium channel blockers, mineralocorticoid receptor antagonists, and calcitonin gene-related peptide receptor antagonists. The chirality at the C4 position of the 1,4-DHP core critically influences its pharmacological activity. Recent advances in asymmetric synthesis, particularly through organocatalysis and transition metal catalysis, have enabled efficient and stereoselective routes to access enantiomerically enriched 1,4-DHP derivatives. However, a comprehensive review summarizing these asymmetric synthetic strategies for this pivotal scaffold is still lacking. This article systematically summarizes recent progress in the asymmetric synthesis of 1,4-DHPs, focusing on catalytic systems involving organocatalysts and transition metal complexes. It further highlights their significant potential in constructing key chiral intermediates for pharmaceutical development, aiming to provide novel perspectives for the research and development of chiral 1,4-DHP-based drugs.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 7","pages":"e202500894"},"PeriodicalIF":2.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687079","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 : 2026-04-14DOI: 10.1002/cbic.202500957
Ola Bartolik, Wenjing Wang
{"title":"A Single-Chain Light-Activatable Transcriptional Reporter for Fluorescently Tagging Mammalian Cells In Vitro.","authors":"Ola Bartolik, Wenjing Wang","doi":"10.1002/cbic.202500957","DOIUrl":"10.1002/cbic.202500957","url":null,"abstract":"<p><p>Optogenetic tools have revolutionized the control of gene expression with high spatial and temporal resolution. Here we present a Single-chain Light-Activatable Transcriptional Reporter (SLATR), a system capable of fluorescently tagging target cells with minutes of white light stimulation. In its inactive, or dark state, a transcriptional factor is cytosolically bound, preventing nuclear translocation. White light irradiation triggers its release through the protease cleavage of a site that is sterically caged by the circularly permuted Avena sativa LOV2 (cpAsLOV2) domain. We discovered that cpAsLOV2 cages the cleavage site more efficiently than AsLOV2, achieving low background in the SLATR design. We demonstrate that SLATR exhibits a signal-to-background ratio between 3.4 and 36 and achieves reporter activation within 60 min of light stimulation. Furthermore, SLATR outperforms the only other single-chain light-activatable transcriptional reporter, LAUNCHER, with faster kinetics, greater light sensitivity, and markedly lower background under identical stimulation conditions. Our single-chain light-activatable transcriptional system expands the optogenetic toolkit though providing a simpler system for regulating gene expression with precise spatiotemporal control.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 7","pages":"e202500957"},"PeriodicalIF":2.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669214","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}