ChemBioChemPub Date : 2025-08-14DOI: 10.1002/cbic.202500425
Yuqi Zhou, Yuruo Zhang, Quanjie Lv, Yijun Han, Linxuan Zhang, Gengxin Zhang, Yumo Chen, Kang Sun, Wei Li, Qi Chen, Ke Tao
{"title":"Dual-Functional Antimicrobial and Anticoagulant Coatings: Synergistic Mechanisms, Research Advances, and Translational Challenges","authors":"Yuqi Zhou, Yuruo Zhang, Quanjie Lv, Yijun Han, Linxuan Zhang, Gengxin Zhang, Yumo Chen, Kang Sun, Wei Li, Qi Chen, Ke Tao","doi":"10.1002/cbic.202500425","DOIUrl":"10.1002/cbic.202500425","url":null,"abstract":"<p>The adhesion of biological components such as bacteria, proteins, and platelets on material surfaces triggers biofilm formation and thrombus generation, which leads to severe infections and embolism risks in blood-contacting medical devices. Conventional blood-contacting coatings predominantly focus on singular antibacterial or anticoagulant functions, while clinical demands urgently require surfaces with synergistic \"antibacterial-anticoagulant\" efficacy to address complex biofouling challenges. Recent advancements in dual-functional antibacterial-anticoagulant coatings have achieved notable progress. This review summarizes four representative categories: (1) antimicrobial-dominant antifouling coatings, which combine active bactericidal mechanisms to inhibit biofilm formation with passive antifouling strategies to suppress thrombogenesis; (2) anticoagulant-loaded bifunctional coatings, merging sustained-release anticoagulant agents with antibacterial active components or antifouling layers to achieve dual active defense; (3) physically biomimetic bifunctional coatings, leveraging micro/nanotopological architectures and surface chemical mimicry to disrupt bacterial adhesion and platelet activation simultaneously; and (4) environment-responsive smart coatings, enabling stimuli-responsive dynamic switching of antibacterial functions to adapt to in vivo microenvironmental changes. This review discusses the design principles and operational mechanisms of coatings while highlighting persistent challenges. Future research should focus on precisely functionalizing interfaces, enhancing synergistic properties, and optimizing dynamic adaptability to promote their practical applications.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854010","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 : 2025-08-14DOI: 10.1002/cbic.202500415
Biswaranjan Baliarsingh, Nandita Madhavan
{"title":"Selective and pH-Responsive Macrocyclic Anionophores","authors":"Biswaranjan Baliarsingh, Nandita Madhavan","doi":"10.1002/cbic.202500415","DOIUrl":"10.1002/cbic.202500415","url":null,"abstract":"<p>The ability to selectively control ion transport across membranes is central for identifying synthetic ionophores that can potentially be used as therapeutics for diseases involving dysfunction of natural ion transporters. Herein, a family of <i>C</i><sub>2</sub>-symmetric macrocycles is presented, which is derived from serine or threonine and a disubstituted aromatic moiety. The ion transport behavior of the macrocycles can be precisely tuned by modifying their aromatic core and symmetry. The phenyl-based macrocycles are highly anion-selective and do not disturb vesicular pH gradients, a key step toward safe therapeutic use of ionophores with minimal cytotoxic risk. In contrast, the introduction of pH responsive pyridyl units in the macrocycle results in measurable chloride transport only below pH 5, a feature that can be utilized to target the acidic lysosomal compartments. This work highlights a structure-guided approach to achieving tunable and conditionally active ionophores, with potential implications in biomedical applications.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854017","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":"Lacmoid-Induced Conformational Changes Inhibit Fibrillation of Human Islet Amyloid Polypeptide","authors":"Charu Thapliyal, Prachi Joshi, Masochon Raingam, Rajesh Mishra","doi":"10.1002/cbic.202500383","DOIUrl":"10.1002/cbic.202500383","url":null,"abstract":"<p>Type 2 diabetes is a devastating metabolic disorder affecting millions of people worldwide. Deposition of amyloid formed by human islet amyloid polypeptide (IAPP) around pancreatic β-cells is one of the possible causes of the disease. IAPP is a 37-residue peptide expressed by the pancreatic β-cells and cosecreted with insulin, and its misfolding and aggregation into toxic amyloid fibrils are closely linked to β-cell dysfunction. Herein, it is demonstrated that lacmoid effectively inhibits IAPP fibrillation and disaggregates preformed fibrils. Thioflavin T fluorescence in combination with morphological analysis by atomic force microscopy and transmission electron microscopy confirms complete inhibition and disaggregation of IAPP fibrillation at equimolar concentrations of lacmoid. Additionally, circular dichroism and Fourier transform infrared spectroscopy reveal significant changes in the secondary structure of IAPP during fibrillation in the presence of lacmoid. Cytotoxicity assay in U2OS cells show that lacmoid reduces IAPP fibril-induced toxicity. Molecular docking studies further reveal that the Asn14 residue of IAPP plays a critical role in its interaction with lacmoid. The findings collectively highlight the importance of lacmoid as an inhibitor of IAPP fibrillation which may have potential to develop as a drug candidate for the treatment of type 2 diabetes.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854013","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 : 2025-08-14DOI: 10.1002/cbic.202500359
Seung Hoon An, Hyun Ji Kang, Bong-Gyu Kim, Joong-Hoon Ahn
{"title":"Microbial Synthesis of Six Rosmarinic Acid Derivatives","authors":"Seung Hoon An, Hyun Ji Kang, Bong-Gyu Kim, Joong-Hoon Ahn","doi":"10.1002/cbic.202500359","DOIUrl":"10.1002/cbic.202500359","url":null,"abstract":"<p>Rosmarinic acid (RA) is a phytochemical that exhibits a variety of biological activities. The biological synthesis pathway of RA has been well-established in plants. In this study, the shikimate pathway is engineered to enhance the availability of precursor substrates and the biosynthetic pathway is reconstructed to produce six RA derivatives: <i>p</i>-coumaroyl phenyllactic acid (PPLA), <i>p</i>-coumaroyl 4-hydroxyphenyllactic acid (P4PLA), caffeoyl phenyllactic acid (CPLA), <i>p</i>-coumaroyl salvinic acid (PSA), rosmarinic acid (RA), and isorinic acid (IA). To identify the optimal method for maximizing the production of the target compounds while minimizing the formation of unwanted byproducts, single-cell, stepwise, and coculture approaches are employed. Using the single-cell method, 145.1 mg L<sup>−1</sup> of PPLA and 361.6 mg L<sup>−1</sup> of P4PLA are synthesized. The stepwise method yields 28.0 mg L<sup>−1</sup> of CPLA, 23.4 mg L<sup>−1</sup> of PSA (which contains synthesized IA), and 10.9 mg L<sup>−1</sup> of RA. Finally, the coculture method results in the synthesis of 40.2 mg L<sup>−1</sup> of IA (which contains synthesized PSA).</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854015","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 : 2025-08-14DOI: 10.1002/cbic.202500430
Wei-Lin Ye, Jing Jiang, Gao Li
{"title":"Modulating the Aggregation of Amyloid Proteins by Silica Nanoparticles","authors":"Wei-Lin Ye, Jing Jiang, Gao Li","doi":"10.1002/cbic.202500430","DOIUrl":"10.1002/cbic.202500430","url":null,"abstract":"<p>The aggregation and deposition of amyloid proteins are considered key contributors to the pathogenesis of various diseases. In recent years, a variety of nanoparticles have been employed to modulate amyloid protein aggregation. Among them, silica nanoparticles (SNs) have emerged as particularly promising due to the excellent biocompatibility of silicon-based materials and their favorable physicochemical properties, offering significant therapeutic potential. This review summarizes recent studies on the use of SNs to regulate the aggregation of amyloid proteins. The effects of different types and surface-modified SNs on the aggregation behavior of various amyloid proteins are systematically compared, aiming to provide valuable insights for future research and potential therapeutic applications.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854016","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 : 2025-08-13DOI: 10.1002/cbic.202500357
Nachuan Song, Lijun Wang, Le Zhang, Gengqi Tian, Chi Yao, Dayong Yang
{"title":"Precision Delivery of CRISPR/Cas Systems via DNA Nanostructures for Gene Therapy and Intracellular Detection.","authors":"Nachuan Song, Lijun Wang, Le Zhang, Gengqi Tian, Chi Yao, Dayong Yang","doi":"10.1002/cbic.202500357","DOIUrl":"https://doi.org/10.1002/cbic.202500357","url":null,"abstract":"<p><p>The CRISPR/Cas system represents a transformative breakthrough in genome editing technology, featuring three principal effector proteins with distinct functionalities: Cas9, which induces site-specific double-strand breaks guided by a single guide RNA, enabling precise gene knockout and knock-in modifications; Cas12, which mediates targeted DNA cleavage through cis-activity while exhibiting nonspecific trans-cleavage of single-stranded DNA, a property exploited for ultrasensitive nucleic acid detection in molecular diagnostics; and Cas13, an RNA-guided RNase that specifically degrades complementary RNA transcripts, demonstrating significant potential for antiviral therapies and transcriptome regulation. Despite these advances, the clinical translation of CRISPR/Cas systems faces substantial challenges, particularly in achieving efficient and controllable delivery. This reviewsystematically examines current delivery modalities for CRISPR/Cas systems, with particular emphasis on the implementation of DNA-based functional materials as advanced delivery vehicles. The integration of multifunctional DNA nanostructures with diverse CRISPR/Cas systems may facilitate the development of integrated theranostic platforms, thereby advancing precision medicine through synergistic bioengineering approaches.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500357"},"PeriodicalIF":2.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843881","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 : 2025-07-30DOI: 10.1002/cbic.202500433
Oliwier R. Dulawa, Shane M. Coyle, Fiona Walsh, Trinidad Velasco-Torrijos
{"title":"Beyond FimH: Diversity and Relevance of Carbohydrate-Binding Fimbrial Proteins in Escherichia coli","authors":"Oliwier R. Dulawa, Shane M. Coyle, Fiona Walsh, Trinidad Velasco-Torrijos","doi":"10.1002/cbic.202500433","DOIUrl":"10.1002/cbic.202500433","url":null,"abstract":"<p><i>Escherichia coli</i> (<i>E. coli</i>) is responsible for multiple diseases in humans and animals. Many of them are treated with antibiotics; however, the need for new therapies has led to research in alternative treatments. One such approach involves preventing the adherence of <i>E. coli</i> to host cells by inhibiting their adhesins. Adherence is a crucial step of pathogenesis, and bacterial lectins that recognize host glycans play major roles in host cell adhesion. In fact, lectins are the most common bacterial adhesins. The various pathogenic and nonpathogenic <i>E. coli</i> strains express a multitude of lectins, many of which are found on <i>E. coli</i> fimbriae. Current research on lectin inhibition using glycomimetics has produced many mannose-based inhibitors of the uropathogenic <i>E. coli</i> fimbrial lectin FimH. However, only a limited number of synthetic inhibitors are reported for other lectins. In this review, many other cell surface adhesins of <i>E. coli</i> are discussed, focusing on fimbrial lectins. The types of <i>E. coli</i> strains they are found in, their carbohydrate targets, and their binding sites are also discussed. This review aims to highlight the many lectins that can become therapeutic targets to treat <i>E. coli</i> infections in addition to FimH.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740733","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 : 2025-07-30DOI: 10.1002/cbic.202500266
Halana C. Vlaming, Yara Huppelschoten, Rayman T. N. Tjokrodirijo, Peter A. van Veelen, Francesca D’Amico, Kim B. Jensen, Jens Buchardt, Thomas E. Nielsen, Bhavesh Premdjee, Gerbrand J. van der Heden van Noort
{"title":"Selective Lysine Ubiquitination Using Activated Phenol Esters","authors":"Halana C. Vlaming, Yara Huppelschoten, Rayman T. N. Tjokrodirijo, Peter A. van Veelen, Francesca D’Amico, Kim B. Jensen, Jens Buchardt, Thomas E. Nielsen, Bhavesh Premdjee, Gerbrand J. van der Heden van Noort","doi":"10.1002/cbic.202500266","DOIUrl":"10.1002/cbic.202500266","url":null,"abstract":"<p>Ubiquitination of target proteins is an essential post-translational modification influencing a wide variety of cellular processes. Herein, the use of a novel water-soluble acylation reagent based on the 2,4-dichloro-6-sulfonic acid phenol ester of ubiquitin is described for efficient and selective ubiquitin modification of peptides. Under alkaline conditions, this reagent is swift and regioselective toward lysine acylation, while at neutral pH it shows loss of regioselectivity and is able to acylate both lysine and N-terminal modification at reduced speeds. As proof of concept, a model peptide is utilized to demonstrate this strategy, proving to be successful. Then the ubiquitination of a synthetic protein called Fau gene encoded Ubiquitin-like protein (FUBI) is performed under alkaline conditions followed by tandem MS analysis, proving that the selective lysine ubiquitination works to prepare protein–protein conjugates.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740734","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 : 2025-07-29DOI: 10.1002/cbic.202500450
Krishnan Srinivas, Amelia K. Gilio, Mahima Sharma, Lawrence Green, Alexander Ascham, Jack Domenech, Balázs Pogrányi, Jiacheng Li, Scott P. France, Russell D. Lewis, William P. Unsworth, Gideon Grogan
{"title":"Structures of “Tyrosine-IRED” IR91 from Kribbella flavida in Complex with a Reductive Amination Substrate and Product","authors":"Krishnan Srinivas, Amelia K. Gilio, Mahima Sharma, Lawrence Green, Alexander Ascham, Jack Domenech, Balázs Pogrányi, Jiacheng Li, Scott P. France, Russell D. Lewis, William P. Unsworth, Gideon Grogan","doi":"10.1002/cbic.202500450","DOIUrl":"10.1002/cbic.202500450","url":null,"abstract":"<p>Imine reductases with an (<i>S</i>)-preference for the reduction of the model substrate 2-methyl pyrroline typically contain tyrosine in the active site (Y-IREDs) instead of the aspartate present within (<i>R</i>)-selective enzymes (D-IREDs). As with D-IREDs, a subset of Y-IREDs is capable of enabling reductive amination reactions between some ketone and amine partners to give optically active amines with high optical purity. However, structures of Y-IREDs in complex with the substrates and products of the reductive amination have not been forthcoming. Herein, structures of the Y-IRED IR91 from <i>Kribbella flavida</i> in complex with 5-methoxy-2-tetralone, a synthetic precursor to the anti-Parkinson's treatment rotigotine, and also its reductive amination product with methylamine, 5-methoxy-(<i>S</i>)-2-(<i>N</i>-methylamino)-tetralin, are presented. The structures, in combination with mutation and kinetic studies, support a role for tryptophan residue W258 in the activity of the enzyme, possibly in binding of the ketone prior to reaction with methylamine.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726196","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":"Amphiphilicity to α/γ Hybrid Foldamers through Post-Modification at Multiple Sites: Antimicrobial Design and Structure-Function Relationship","authors":"Syed Kabir Hussain Shah, Rahul Maitra, Alpana Boruah, Karma Patel, Payal Chauhan, Shubham Dashora, Nadakath Sreerag, Arup Roy, Sidharth Chopra, Panchami Prabhakaran","doi":"10.1002/cbic.202400940","DOIUrl":"10.1002/cbic.202400940","url":null,"abstract":"<p>Antimicrobial drug design is an active area of research. Drug resistance in microorganisms to conventional antibiotics imposes a huge burden on the healthcare and economy worldwide. Understanding the structural parameters controlling the antimicrobial activity enables researchers to develop effective antimicrobial agents. Post-modification of artificial peptides as a method to introduce amphiphilicity, a structural parameter to exhibit antimicrobial activity, is described in the current work. Using two hybrid sequences composed of 5-amino salicylic acid and natural amino acid leucine (Leu) or phenylalanine (Phe), the approach enabled us to prepare peptides varying in chain length, charge, and cationic groups. The peptides against the ESKAP panel of bacterial pathogens showed a broad spectrum of antibacterial activity. The structure-function relationship indicated that antimicrobial activity varied with chain length, and the peptides composed of Leu residues were more effective than peptides with Phe residues. The late-stage modification and functional diversification can be done at a large scale, and the approach simplifies the synthesis and reduces the cost of production.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726195","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}