ChemBioChem最新文献_第6页

Robotic-Assisted Capture-Systematic Evolution of Ligands by Exponential Enrichment of RNA Aptamers Binding to Small Molecules. 机器人辅助捕获- selex RNA适体结合小分子。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-14 DOI: 10.1002/cbic.202500264

Tjasa Legen, Günter Mayer

{"title":"Robotic-Assisted Capture-Systematic Evolution of Ligands by Exponential Enrichment of RNA Aptamers Binding to Small Molecules.","authors":"Tjasa Legen, Günter Mayer","doi":"10.1002/cbic.202500264","DOIUrl":"10.1002/cbic.202500264","url":null,"abstract":"Due to their small size, stability, and cost-effectiveness compared to antibodies, aptamers developed by systematic evolution of ligands by exponential enrichment (SELEX) are promising candidates for the detection of small molecules. In SELEX, a small target molecule is usually covalently immobilized on a surface to separate bound from unbound nucleic acid sequences. However, this immobilization alters the molecule, that is, additional chemical entities are added and the electron distribution is altered, compromising the enrichment properties. To overcome this problem, a capture SELEX method has been successfully developed in which the RNA or DNA libraries are bound to a surface via a complementary oligodeoxynucleotide, and the soluble ligand is used to capture nucleic acids that bind to it from that surface. Herein, the development of an automated version of the capture SELEX method for the identification of RNA aptamers that bind small molecules is described. This method is fully automated and performs up to 12 iterative selection cycles without manual interference in 72 h. The approach is therefore suitable as rapid route to aptamers and enables resource-efficient test selections to assess \"aptamerogenicity\" of a target.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500264"},"PeriodicalIF":2.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293001","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

Spatiotemporal Analysis of Proteins in Single Live Cells: Methods and Applications. 单个活细胞中蛋白质的时空分析：方法和应用。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-13 DOI: 10.1002/cbic.202500336

Yanrong Wen, Fenxia Lin, Zhen Liu

引用次数: 0

Activity-Enhancing Mutations in an LmrR-Based Artificial Metalloenzyme Destabilize the Protein Scaffold and Alter its Conformational Plasticity. 基于lmrr的人工金属酶的活性增强突变破坏了蛋白质支架的稳定性并改变了其构象可塑性。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-13 DOI: 10.1002/cbic.202500259

Adil A Safeer, Fabrizio Casilli, Wouter Beugelink, Gerard Roelfes, Marc Baldus, Hugo van Ingen

{"title":"Activity-Enhancing Mutations in an LmrR-Based Artificial Metalloenzyme Destabilize the Protein Scaffold and Alter its Conformational Plasticity.","authors":"Adil A Safeer, Fabrizio Casilli, Wouter Beugelink, Gerard Roelfes, Marc Baldus, Hugo van Ingen","doi":"10.1002/cbic.202500259","DOIUrl":"10.1002/cbic.202500259","url":null,"abstract":"Artificial metalloenzymes (ArM) hold great potential for the sustainable catalysis of complex new-to-nature reactions. To efficiently improve the catalytic efficacy of ArMs, a rational approach is desirable, requiring detailed molecular insight into their conformational landscape. Lactococcal multidrug resistance regulator (LmrR) is a multipurpose ArM scaffold protein that, when bound to the Cu(II)-phenanthroline cofactor, catalyzes the Friedel-Crafts alkylation (FCA) of indoles. Previously, the M8D and A92E mutations are found to increase the efficiency of this reaction, but a molecular explanation has been lacking. The impact of these two activating mutations on the conformational landscape of LmrR in its apo, cofactor- and substrate-bound states is determined. The mutations cause a marked destabilization of the dimerization interface, resulting in a more open central hydrophobic cavity and a dynamic equilibrium between dimer and monomer LmrR is found. While mutant and wild-type have similar pocket conformation in the cofactor-bound state, the mutant shows a distinct interaction with the substrate. Our results suggest that increased retention of the catalytic cofactor and widened plasticity improve the activity of the mutant. Ultimately, these results help elucidating the intricate relationships between conformational dynamics of the protein scaffold, cofactor, and substrates that define catalytic activity.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500259"},"PeriodicalIF":2.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281799","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

Hybrid Crosslinking of Collagen-Mimetic Peptides for Tunable Assembly and Enhanced Biopolymer Encapsulation 模拟胶原蛋白多肽的杂交交联可调组装和增强生物聚合物封装。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-12 DOI: 10.1002/cbic.202500257

Yi-Hong Xiao, Jia-Cherng Horng

{"title":"Hybrid Crosslinking of Collagen-Mimetic Peptides for Tunable Assembly and Enhanced Biopolymer Encapsulation","authors":"Yi-Hong Xiao, Jia-Cherng Horng","doi":"10.1002/cbic.202500257","DOIUrl":"10.1002/cbic.202500257","url":null,"abstract":"Collagen, the most abundant protein in the extracellular matrix of mammals, plays a vital role in maintaining cellular structure. Collagen-mimetic peptides (CMPs), synthetic biopolymers, have emerged as promising materials for biomedical applications because of their excellent biocompatibility, biodegradability, and tunable chemical and physical properties. In this study, a series of CMPs were designed using a Pro-Pro-Gly triplet-based template, incorporating lysine residues for Lys-glutaraldehyde (Lys-GTA) crosslinking and histidine residues for metal-His coordination to facilitate CMP assembly. To modulate the morphology of the assembled structures, peptides of varying lengths were synthesized and histidine residues within the CMP sequence were strategically positioned. Scanning electron microscopy, transmission electron microscopy, and atomic force microscopy confirmed that the designed CMPs assembled into distinct spherical structures under physiological conditions. The fluorescence measurements and confocal microscopy further demonstrated that these peptide-assembled spheres can encapsulate 40 K FITC-Dextran while forming large-scale structures. In summary, an effective strategy for assembling CMPs into higher-order spherical structures is developed by integrating Lys-GTA crosslinking with metal-His coordination. Notably, these assemblies exhibited the capability to encapsulate large biomolecules, offering valuable insights for the design of collagen-based biomaterials.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281801","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

Computational De Novo Design of Group II Introns Yields Highly Active Ribozymes II族内含子的计算从头设计产生高活性核酶。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-12 DOI: 10.1002/cbic.202500356

Deni Szokoli, Noemi E. Nwosu, Lukas M. Glatt, Hannes Mutschler

{"title":"Computational De Novo Design of Group II Introns Yields Highly Active Ribozymes","authors":"Deni Szokoli, Noemi E. Nwosu, Lukas M. Glatt, Hannes Mutschler","doi":"10.1002/cbic.202500356","DOIUrl":"10.1002/cbic.202500356","url":null,"abstract":"Group II introns (G2Is) are large self-splicing ribozymes with emerging potential in biotechnological applications. Despite growing interest, their complexity has so far precluded efforts to design them from scratch. While computational approaches have enabled the design of small RNA catalysts, methods for engineering large ribozymes remain underdeveloped. Herein, the RNA inverse folding algorithm aRNAque is used to design G2Is from scratch, yielding three novel self-splicing ribozymes with unusually stable structures. The designed intron Arq.I2 is revealed to be an unexpectedly proficient ribozyme in vitro, self-splicing at a rate comparable to the fastest known G2Is. While most G2Is are believed to be inactive under intracellular conditions in the absence of maturase proteins, it is shown that Arq.I2 self-splices in Escherichia coli cells. The results demonstrate that highly active variants of large and complex ribozymes can be designed de novo with relative ease using existing inverse folding algorithms, paving the way for the design of bespoke ribozymes derived from G2Is for the development of biotechnological tools.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500356","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273771","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}

引用次数: 0

Chemoenzymatic Route toward a De Novo Enantioselective Total Synthesis of (S)-Baclofen Based on Metal-Catalyzed Hydroformylation and Enzymatic Transamination. 基于金属催化氢甲酰化和酶转氨化的(S)-巴氯芬从头对映选择性全合成的化学酶途径。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-12 DOI: 10.1002/cbic.202500108

Feodor Belov, Hannah Bork, Luise Hänel, Manideep V Kollipara, Matthias Höhne, Harald Gröger, Jan von Langermann

引用次数: 0

Characterization of DnaB–DnaG Interaction in M. tuberculosis Using Small-Angle X-ray Scattering-Based Dissociation Assay 利用基于saxs的解离试验表征结核分枝杆菌中dna - dnag相互作用。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-11 DOI: 10.1002/cbic.202500289

Dayan A, Ilic S, Akabayov B

引用次数: 0

Chemoenzymatic Synthesis of 3-Halochromones via Oxidative α-Halogenation of Enaminones in TPGS-750-M Micelles TPGS-750-M胶束中胺酮氧化α-卤化合成3-卤代酮的化学酶法研究。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-11 DOI: 10.1002/cbic.202500277

Chisanu Krongyut, Jakkarin Limwongyut, Nittaya Wiriya, Anyanee Kamkaew, Ailada Jantasin, Rung-Yi Lai

{"title":"Chemoenzymatic Synthesis of 3-Halochromones via Oxidative α-Halogenation of Enaminones in TPGS-750-M Micelles","authors":"Chisanu Krongyut, Jakkarin Limwongyut, Nittaya Wiriya, Anyanee Kamkaew, Ailada Jantasin, Rung-Yi Lai","doi":"10.1002/cbic.202500277","DOIUrl":"10.1002/cbic.202500277","url":null,"abstract":"Synthesis strategies of chromones have been widely investigated due to the abundance of chromone moiety in bioactive compounds and natural products. Of which, 3-halochromones are a versatile set of precursors to synthetically access valuable compounds with chromone frameworks. Generally, 3-halochromones are synthesized from o-hydroxy enaminones through oxidative α-halogenation, a process that often uses toxic and corrosive chemicals. Herein, an alternative strategy is presented for oxidative α-halogenation catalyzed by vanadium-dependent chloroperoxidase from Curvularia inaequalis (CiVCPO) with H2O2/KX (X = Cl, Br, and I) in an aqueous medium. With a micellar system from a surfactant TPGS-750-M, substrate concentration can be increased to 50 mM without compromising the yield, thereby, significantly reducing the use of organic solvents. Substrate scope investigation reveals that bromination and chlorination processes prefer electron-donating substituents although moderate electron-withdrawing groups are tolerated (20 examples). Additionally, iodination processes can be performed under the optimized condition. However, slow conversion indicates that further optimization is needed. It is also found that iodination can occur without CiVCPO, albeit at a lower conversion. Further investigation suggests that such a conversion took place via I2 generated in situ. Overall, this chemoenzymatic method can offer an environmentally friendly approach to access a variety of 3-bromo or 3-chlorochromones.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264932","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

Rational Design and Bioactive Screening of Peptide Inhibitors Targeting Host-Pathogen Interactions in Severe Fever with Thrombocytopenia Syndrome Virus. 针对发热伴血小板减少综合征病毒（SFTSV）宿主-病原体相互作用肽抑制剂的合理设计和生物活性筛选

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-10 DOI: 10.1002/cbic.202500296

Lixin Yang, Zhipeng Hu, Tingting Zhou, Dan Wang, Jie Xu, Naiwen Zhang, Dongbo Tang, Yifang Han, Hai Qian, Wei Shi

{"title":"Rational Design and Bioactive Screening of Peptide Inhibitors Targeting Host-Pathogen Interactions in Severe Fever with Thrombocytopenia Syndrome Virus.","authors":"Lixin Yang, Zhipeng Hu, Tingting Zhou, Dan Wang, Jie Xu, Naiwen Zhang, Dongbo Tang, Yifang Han, Hai Qian, Wei Shi","doi":"10.1002/cbic.202500296","DOIUrl":"10.1002/cbic.202500296","url":null,"abstract":"Severe fever with thrombocytopenia syndrome virus (SFTSV) poses a significant threat to public health, with limited therapeutic options available. This study focuses on the rational design and screening of peptide inhibitors targeting host-pathogen interactions, specifically between the viral Gn glycoprotein and key host cell receptors, DC-SIGN and NMMHC-IIA. By employing molecular dynamics simulations, alanine scanning, and peptide docking techniques, peptides were designed to disrupt these protein-protein interactions. Among the synthesized candidates, peptides II-1 and II-4 demonstrate potent inhibitory activity against SFTSV infection, with reduced TCID50 values in cellular assays and displayed exceptional affinity (KD = 7.381 × 10-8 M, 1.439 × 10-8 M), These peptides also exhibit low cytotoxicity and hemolytic toxicity, highlighting their safety profile. Molecular dynamics simulations confirm strong binding affinities for these peptides, underpinned by stable hydrogen bonding interactions. This research provides a promising platform for developing peptide-based therapeutics targeting SFTSV, paving the way for further preclinical evaluation and clinical applications.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500296"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256901","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

α-Synuclein Sequences from Long-Lived Animals Display Generally Diminished Aggregation Compared to Shorter-Lived Animals Including Humans 与包括人类在内的寿命较短的动物相比，长寿动物α-突触核蛋白序列的聚集性普遍降低。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-10 DOI: 10.1002/cbic.202500340

Gilbert B. Ampomah, Eldon R. Hard, Matthew R. Pratt

{"title":"α-Synuclein Sequences from Long-Lived Animals Display Generally Diminished Aggregation Compared to Shorter-Lived Animals Including Humans","authors":"Gilbert B. Ampomah, Eldon R. Hard, Matthew R. Pratt","doi":"10.1002/cbic.202500340","DOIUrl":"10.1002/cbic.202500340","url":null,"abstract":"The overall process of protein aggregation from soluble species to amyloid fibrils is toxic to neurons and can propagate along neuronal connections in ways that potentially explain the pathological progression in most neurodegenerative diseases. One of these aggregation-prone proteins is α-synuclein (α-Syn), which forms insoluble protein deposits in Parkinson's disease and other synucleinopathies. The majority of cases of Parkinson's disease occur fairly late in life, and even early-onset variants of the disease caused by mutations to α-Syn occur toward the end of the lifespan for prehistoric man. This suggests a lack of evolutionary pressure to prevent protein aggregation in animals with similar or shorter lifespans. However, α-Syn is also found in animals with notably longer lifespans. Here, this study tests the aggregation propensity of α-Syn sequences from short- and longer-lived animals at a range of evolutionary distances from humans. This study finds that, in general, longer-lived animals display slower α-Syn aggregation kinetics and the formation of smaller and less uniform fibrils. Overall, data indicate that some evolutionary pressure may have existed for preventing α-Syn aggregation, but that pressure is lost in the more recent branch of shorter-lived animals containing humans.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264934","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