ChemBioChemPub Date : 2025-04-04DOI: 10.1002/cbic.202500122
Mussarat Tasleem, Asaad Mohamad Matouk, Manzar Abbas
{"title":"Design of Short Peptides for the Reduction of Silver Ions and Stabilization of Nanocomposites in Combating Bacterial Infections.","authors":"Mussarat Tasleem, Asaad Mohamad Matouk, Manzar Abbas","doi":"10.1002/cbic.202500122","DOIUrl":"https://doi.org/10.1002/cbic.202500122","url":null,"abstract":"<p><p>Combating bacterial infections has become a formidable challenge in healthcare due to the rise of antibiotic resistance. Recently, short peptide-based nanobiomaterials, assembled through silver metal and peptide building blocks, have emerged as promising antibiotic agents for treating resistant bacterial infections. In this minireview, recent advances in silver-peptide nanocomposites are highlighted, both with and without the assistance of UV or sunlight, for antibacterial applications. The chemical design of biomolecules such as amphiphilic short peptides, amino acids, and oligopeptides plays a crucial role in the reduction, stabilization, and biocompatibility of silver-peptide nanocomposites. Noncovalent interactions involved in the formation of nanocomposites are explored in the context of the structure-function relationship. The antibacterial activities and underlying mechanisms, which depend on specific peptide building blocks, are also reviewed. Finally, the conclusion and the outlook provide insights into the design of novel peptide building blocks for the development of silver-peptide nanocomposites with enhanced antibacterial activities.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500122"},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778736","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 : 2025-04-04DOI: 10.1002/cbic.202500134
Thomas J C Carraro, Samrat Dasgupta, Jacqueline Ku, Shane R Thomas, Louis M Rendina
{"title":"Boron-Based Functionalities Enhance, the Potency of 2,5-Dimethylfuran-Based IDO1 Inhibitors.","authors":"Thomas J C Carraro, Samrat Dasgupta, Jacqueline Ku, Shane R Thomas, Louis M Rendina","doi":"10.1002/cbic.202500134","DOIUrl":"https://doi.org/10.1002/cbic.202500134","url":null,"abstract":"<p><p>Indoleamine-2,3-dioxygenase-1 (IDO1) is a critical immunoregulatory enzyme responsible for the metabolism of tryptophan during inflammation and disease. Based on a 2,5-dimethylfuran framework, examples of indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors containing a diverse set of boron-based functional groups (closo-1,2- and 1,7-carborane, boronic acids and esters, and benzoxaboroles) are reported. The novel boron derivatives display low micrometer affinity for the human recombinant enzyme, with IC50 values ranging from 8 to 60 μM. Superior results are observed for the closo-carborane compounds which demonstrate a significant improvement in potency over their phenyl analogues, with inhibition of the IDO1 enzyme increasing by up to ≈80%.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500134"},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778774","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 : 2025-04-04DOI: 10.1002/cbic.202500076
Reuben B Leveson-Gower
{"title":"Designing Enzymatic Reactivity with an Expanded Palette.","authors":"Reuben B Leveson-Gower","doi":"10.1002/cbic.202500076","DOIUrl":"https://doi.org/10.1002/cbic.202500076","url":null,"abstract":"<p><p>The expanding applications of biocatalysis in the chemical and pharmaceutical sectors herald a greener future for these industries. Yet, the range of chemical reactions known to enzymes only covers a small fraction of what is required for modern synthetic routes. To continue the increases in sustainability afforded by converting chemical processes into enzymatic ones, fundamentally new kinds of biocatalytic reactivity are required. Perhaps the very components from which enzymes are constructed, a palette of canonical amino acids and cofactors, inherently limit their catalytic possibilities, even if all the available natural sequence space can be explored. In recent years, there has been an explosion of strategies to produce new biocatalytic function through the incorporation of noncanonical amino acids and synthetic cofactors, new colors which are added to the enzyme design palette. This has enabled new enzymatic reactions that proceed via organocatalytic, organometallic, and photocatalytic mechanisms. Aside from designing new enzymatic activities from scratch, exogenous photocatalysts have recently also been used in synergy with natural enzyme active sites to diverge their reactivity towards radical pathways. This review will highlight recent developments in enriching enzymatic chemistry with new unnatural components, providing an outlook for future directions and needed developments for practicality and sustainability.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500076"},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778741","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 : 2025-04-04DOI: 10.1002/cbic.202500024
Conor Pulliam, Lukuan Hou, Dan Xue, Mingming Xu, Katherine Holandez-Lopez, Jie Li
{"title":"A Bacterial Sulfotransferase Catalyzes an Unusual Di-Sulfation in Natural Products Biosynthesis.","authors":"Conor Pulliam, Lukuan Hou, Dan Xue, Mingming Xu, Katherine Holandez-Lopez, Jie Li","doi":"10.1002/cbic.202500024","DOIUrl":"https://doi.org/10.1002/cbic.202500024","url":null,"abstract":"<p><p>Sulfation is a widely used strategy in nature to modify the solubility, polarity, and biological activities of molecules. The enzymes catalyzing sulfation, sulfotransferases (STs), are typically highly specific to a single sulfation site in a molecule. Herein, the identification and characterization of sulfated adipostatins is reported and reveals a novel sulfotransferase, AdpST, which is responsible for di-sulfation at two sites of adipostatins. The initial bioinformatic analysis in search of adipostatin analogs from Streptomyces davaonensis DSM101723 identifies adpST and a 3'-phosphoadenosine-5'-phosphosulfate (PAPS) biosynthetic cassette, which are co-clustered with the adipostatin-encoding type III polyketide synthase. Mono- and di-sulfated adipostatin analogs are discovered in the extracts of S. davaonensis DSM101723, whereas di-sulfated bacterial natural products has not been reported. Using a series of in vivo and in vitro experiments, it is confirmed that AdpST is solely responsible for both mono- and di-sulfation of adipostatins, a catalytic activity which has not been identified in bacterial PAPS-dependent STs to date. It is further demonstrated that the dedicated PAPS biosynthetic cassette improves di-sulfation capacity. Lastly, it is determined that AdpST shares similarity with a small group of uncharacterized STs, suggesting the presence of additional unique bacterial STs in nature, and that AdpST is phylogenetically distant from many characterized STs.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500024"},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778735","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 : 2025-04-04DOI: 10.1002/cbic.202500170
Wenyuan Li, Srinivas R Paladugu, Jordan P Liles, Manju Karthikeyan, Kevin Chase, Shrinivasan Raghuraman, Matthew S Sigman, Ryan E Looper
{"title":"Macrocycles of Saxitoxin: Insights into the Structure of Zetekitoxin AB.","authors":"Wenyuan Li, Srinivas R Paladugu, Jordan P Liles, Manju Karthikeyan, Kevin Chase, Shrinivasan Raghuraman, Matthew S Sigman, Ryan E Looper","doi":"10.1002/cbic.202500170","DOIUrl":"https://doi.org/10.1002/cbic.202500170","url":null,"abstract":"<p><p>Zeteketoxin AB is the only macrocyclic member of the bis-guanidinium ion toxins, and the only member reported to be more potent than the parent (+)-saxitoxin. A rationale for this exquisite potency remains difficult to develop due to the scarcity of natural material and a lack of consensus around the specific structure of the toxin itself. A strategy is reported, leveraging an intramolecular Michael addition to forge macrocycles bridging the saxitoxin core, mimicking the proposed structure of zetekitoxin AB. Intriguingly, these analogs do not form a hydrate at C12. Experimental and computational studies suggest that a macrocyclic framework destabilizes the hydrate, casting doubt on the presence of a macrocycle in zetekitoxin. Preliminary activity screening utilizing calcium imaging-based constellation pharmacology demonstrates several analogs to have potent pharmacological activity similar to (+)-saxitoxin despite the lack of the C12 hydrated ketone.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500170"},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778744","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":"Bioorthogonal Post-Labeling Reveals Nuclear Localization of a Highly Cytotoxic Half-sandwich Ir(III) Tetrazine Complex in Live Cells.","authors":"Alfonso Annunziata, Sadek Amhaz, Jérémy Forté, Geoffrey Gontard, Romain Morichon, Joëlle Sobczak-Thépot, Michele Salmain","doi":"10.1002/cbic.202500090","DOIUrl":"https://doi.org/10.1002/cbic.202500090","url":null,"abstract":"<p><p>Intracellular imaging of anticancer metallodrugs often relies on pre-labeling with organic fluorophores, which significantly affects their physicochemical properties and intracellular distribution. On the other hand, the reported post-labeling strategies based on click-chemistry reactions require cell fixation and permeabilization. Here, we present a post-labeling approach based on the catalyst-free, inverse electron-demand Diels-Alder reaction (iEDDA) between a strained fluorescein-tagged bicyclononyne derivative (BCN-FAM) and half-sandwich Ir(III) complexes containing bidentate ligands comprising a tetrazine (Tz-R,R') entity. Five half-sandwich Ir(III) complexes with formula [Cp*Ir(Tz-R,R')Cl]0/+ have been synthesized and fully characterized, including the X-ray crystal structures of three of the five derivatives. Investigations of their stability and their reactivity in aqueous solution and in a model iEDDA reaction revealed the strong influence of the tetrazine ligand structure on the chemical properties of the corresponding complexes. A highly cytotoxic metallodrug candidate (Ir-C,NPh,Me) was identified from biological studies, and chemical reactivity studies disclosed an unusual preference for binding of methionine over cysteine. Post-labeling of Ir-C,NPh,Me in live HeLa cells highlighted its preferential accumulation within the nucleus, suggesting its retention through covalent modifications of nuclear proteins in good agreement with other half-sandwich iridium(III) complexes.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500090"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771073","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 : 2025-04-03DOI: 10.1002/cbic.202500176
Chao Liao, Hengrun Li, Haotian Zheng, Chaofeng Li, Liangxu Liu, Jiawei Wang, Jun Ni
{"title":"Optimization and Application of the Purified Cell-free System.","authors":"Chao Liao, Hengrun Li, Haotian Zheng, Chaofeng Li, Liangxu Liu, Jiawei Wang, Jun Ni","doi":"10.1002/cbic.202500176","DOIUrl":"https://doi.org/10.1002/cbic.202500176","url":null,"abstract":"<p><p>Cell-free protein synthesis (CFPS) is extensively applied in biotechnological research. Unlike the lysate-based CFPS system, the alternative purified cell-free system, Protein synthesis Using Recombinant Elements (PURE), has garnered a great attention due to its controllability and flexibility of adjusting individual component for in vitro transcription and translation research. The PURE system has been widely studied in the synthetic biological field, and optimized for its application in prototyping research, non-canonical amino acid incorporation and synthetic cell construction. Herein, we discuss the recent optimization strategies for a simple and enhanced PURE system. In addition, the recent application via the PURE system and the current challenges for the development of a more robust and controllable PURE are highlighted.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500176"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778747","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 : 2025-04-03DOI: 10.1002/cbic.202500044
Alexander Kai Buell
{"title":"Induction and manipulation of biomolecular condensates through spatially heterogeneous solution conditions.","authors":"Alexander Kai Buell","doi":"10.1002/cbic.202500044","DOIUrl":"https://doi.org/10.1002/cbic.202500044","url":null,"abstract":"<p><p>The study of biomolecular condensates (BMCs) is of great current interest because of the proposed roles of these types of assemblies in biological function and disease. In living cells, BMCs form in a highly heterogeneous environment and are influenced by concentration gradients of various relevant species. Furthermore, the biological functionality of the BMCs requires precise spatial control of their formation in some cases. In recent years, a number of in vitro experimental approaches have emerged that allow the generation, study and manipulation of BMCs through the creation of well-defined spatially heterogeneous solution conditions relevant for BMC formation. In this Concept article I will present in what way such methods can contribute to improved understanding and control of BMCs.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500044"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771078","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":"Phase separation in biochemical and biological systems: Implications for disease pathogenesis.","authors":"Raj Dave, Kshipra Pandey, Ritu Patel, Raghu Solanki, Nidhi Gour, Dhiraj Bhatia","doi":"10.1002/cbic.202400883","DOIUrl":"https://doi.org/10.1002/cbic.202400883","url":null,"abstract":"<p><p>Phase separation is the phenomenon where distinct liquid phases within solution, play a critical role in the organization and function of biomolecular condensates within cells. Dysregulation of phase separation has been implicated, which can be witnessed in various diseases including neurodegenerative disorders, metabolic syndromes, and cancer. This review provides a comprehensive analysis of the role of phase separation in disease pathogenesis, which focuses on single amino acids, carbohydrates, and nucleotides. Molecular mechanisms underlying phase separation are also discussed with specific examples of diseases associated with dysregulated phase separation. Furthermore, consideration of therapeutic strategies targeting phase separation for disease intervention is explored.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400883"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778756","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 : 2025-04-01DOI: 10.1002/cbic.202500112
Nermina Malanovic, Aden Hodzic, Djenana Vejzovic, Altea Topciu, Kirill Kuhlmann, Raj Kumar, Maria Andrea Mroginski, Alejandra Andrea de Miguel, Pia Hofmann, Klaus Zangger, Markus Weingarth, Robert A Cordfunke, Jan W Drijfhout, Peter Nibbering, Michal Belicka, Karl Lohner
{"title":"SAAP-148 oligomerizes into a hexamer forming a hydrophobic inner core.","authors":"Nermina Malanovic, Aden Hodzic, Djenana Vejzovic, Altea Topciu, Kirill Kuhlmann, Raj Kumar, Maria Andrea Mroginski, Alejandra Andrea de Miguel, Pia Hofmann, Klaus Zangger, Markus Weingarth, Robert A Cordfunke, Jan W Drijfhout, Peter Nibbering, Michal Belicka, Karl Lohner","doi":"10.1002/cbic.202500112","DOIUrl":"https://doi.org/10.1002/cbic.202500112","url":null,"abstract":"<p><p>Human cathelicidin LL-37 is a widely studied antimicrobial 37-mer peptide with various ascribed functions, that serves as a template for designing novel peptides. Its derivative, the 24-mer SAAP-148, is highly effective in vitro in eradicating multidrug-resistant bacteria, persistent cells, and biofilms, without inducing resistance. SAAP-148 is characterized by a high cationic charge (+11) and 46% hydrophobicity, which, once the peptide folds into an alpha helix, forms a wide hydrophobic face. This highly amphipathic nature facilitates on the one hand its insertion into the membrane's fatty acyl chain region and on the other hand it´s interaction with anionic membrane components, which contributes to its mode of action in killing bacteria. However, the contributions of the secondary and quaternary structures remain underexplored. To address this, we conducted a study using anionic and zwitterionic membrane models, applying circular dichroism, NMR spectroscopy, X-ray scattering, AlphaFold 3 and molecular dynamics simulations. Our results reveal that SAAP-148 adopts a stable hexameric bundle composed of three parallel dimers, creating a hydrophobic core of aromatic residues. This structure is retained at the membrane interface, where MD simulations suggest the formation of a fiber-like structure on anionic membranes, most likely driven by exposed cationic side chains.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500112"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750459","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}