IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-16 DOI: 10.1002/cbic.202500343

James Luccarelli, Philip C Simister, Andrew D Hamilton, Stephan M Feller, Sam Thompson

{"title":"A Polyproline type II Peptidomimetic Disrupts a Grb2 SH3C Domain Protein-protein Interaction Implicated in Breast Cancer.","authors":"James Luccarelli, Philip C Simister, Andrew D Hamilton, Stephan M Feller, Sam Thompson","doi":"10.1002/cbic.202500343","DOIUrl":"https://doi.org/10.1002/cbic.202500343","url":null,"abstract":"Given the essential role of protein-protein interactions (PPIs) in cellular signalling pathways their selective modulation is of great therapeutic interest. Mimicry of secondary structural protein elements has emerged as a promising strategy, with various scaffolds reproducing recognition surfaces of α-helical and β-strand/sheet proteins. A critical PPI, controlling cell growth and proliferation in breast and other cancers, occurs between Grb2 and a polyproline II (PPII) helix embedded in Gab2. Herein, we present the first example of a general approach for non-peptidic mimicry of extended PPII helices and demonstrate that the scaffold may be functionalised to recapitulate the binding characteristics of crucial hydrophobic and cationic Gab2 hot-spot side-chains. The rationally-designed peptidomimetic binds Grb2 at the same position as Gab2 (protein-observed NMR) with affinities comparable to the native peptide sequence (SPR). With the addition of a new polyproline II minimalist scaffold these studies further validate the use of diverse secondary structure peptidomimetics in disrupting therapeutically relevant PPIs.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500343"},"PeriodicalIF":2.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075103","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

Changes in the Aqueous Solvent do not Impact the Internal Ring Flip Dynamic of Fully Buried F52 in Protein GB1. 水溶液的变化不影响蛋白GB1中完全埋藏的F52的内环翻转动力学。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-16 DOI: 10.1002/cbic.202500183

Matthias Dreydoppel, Mikhail Achkinazi, Charlotte Krünholz, Paula L Jordan, Ulrich Weininger

引用次数: 0

Photoinduced Ene-Reductase Catalysis via EDA Complexes. 通过EDA配合物的光诱导酶还原酶催化。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-15 DOI: 10.1002/cbic.202500329

Jian Xu, Shuang Liu, Runmiao Yang

引用次数: 0

Amino Acid-based Self-Assembled Supramolecular Structures: From Pathological Implications to Biomedical Applications. 基于氨基酸的自组装超分子结构：从病理意义到生物医学应用。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-14 DOI: 10.1002/cbic.202500228

Pooja Sharma, Prabhjot Singh, Neelam Neelam, Nishima Wangoo

{"title":"Amino Acid-based Self-Assembled Supramolecular Structures: From Pathological Implications to Biomedical Applications.","authors":"Pooja Sharma, Prabhjot Singh, Neelam Neelam, Nishima Wangoo","doi":"10.1002/cbic.202500228","DOIUrl":"https://doi.org/10.1002/cbic.202500228","url":null,"abstract":"Self-assembly is defined as a spontaneous ordering of molecules into distinct supramolecular structures similar to the naturally occurring biomolecules such as DNA, lipids and proteins. Interestingly, this strategy has gained huge importance in recent decades, leading to substantial advancements in the biomedical field, including drug delivery, biosensing, tissue engineering, etc. The unique role of \"FF\" moiety in promoting self-aggregation in larger proteins is well established owing to its frequent occurrence in amyloids. This finding came as a breakthrough in peptide nanotechnology research leading to the exploration of various peptide-based supramolecular structures demonstrating exceptional functional roles with futuristic applications. In this regard, since amino acids are the building blocks of peptides, the detailed investigation and discussion regarding their self-assembly behavior are expected to provide important insights into designing advanced functional materials from amino acids and peptides. This review provides a systematic overview of various latest findings on amino-acid-based self-assembly and its pathological as well as functional role. The review also highlights the importance of emerging applications from self-assembled amino-acid-based nanomaterials in the field of material science and biomedicine.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500228"},"PeriodicalIF":2.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956062","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

Photoactivatable Alkyne Tag for Photolabeling Biomolecules in Living Cells. 活细胞中生物分子光标记的光活化炔标签。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-14 DOI: 10.1002/cbic.202500190

Yuki Umeda, Hao Zhu, Satoshi Yamaguchi, Sho Nakamura, Masato Takada, Shin Izuta, Akimitsu Okamoto

{"title":"Photoactivatable Alkyne Tag for Photolabeling Biomolecules in Living Cells.","authors":"Yuki Umeda, Hao Zhu, Satoshi Yamaguchi, Sho Nakamura, Masato Takada, Shin Izuta, Akimitsu Okamoto","doi":"10.1002/cbic.202500190","DOIUrl":"https://doi.org/10.1002/cbic.202500190","url":null,"abstract":"Light-induced molecular imaging methods have attracted considerable attention owing to their potential for monitoring changes in the localization of intracellular molecules, which can provide valuable insights into the molecular mechanisms of living systems. In this study, a photoactivatable alkyne tag is developed by modifying an unstable intermediate of the alkyne-forming reaction with a photodegradable protecting group; the photodegradation triggers the conversion of the intermediate into a linear alkyne in an aqueous solution. The developed photoactivatable alkyne tag is incorporated into a cholesterol analog, introduced into living cells, and exposed to a biocompatible dose of 365 nm light. Subsequently, the cholesterol analog in light-irradiated cells is microscopically visualized through alkyne-specific biotinylation via copper-catalyzed azide-alkyne cycloaddition and biotin-specific labeling with fluorescence-labeled streptavidin. The obtained results indicate that the photoactivatable alkyne tag can be photoconverted into alkyne derivatives inside cells and applied to the light-induced intracellular imaging of biomolecules. This photoactivatable chemical tag can potentially expand the range of applications of light-induced molecular imaging of various biomolecules.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500190"},"PeriodicalIF":2.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075146","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

A thermostable bacterial metallohydrolase that degrades organophosphate plasticizers. 一种耐热的细菌金属水解酶，能降解有机磷增塑剂。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-13 DOI: 10.1002/cbic.202500055

Dawei Ji, Rebecca Frkic, Javad Deylami, Joachim Larsen, Matthew Spence, Colin Jackson

{"title":"A thermostable bacterial metallohydrolase that degrades organophosphate plasticizers.","authors":"Dawei Ji, Rebecca Frkic, Javad Deylami, Joachim Larsen, Matthew Spence, Colin Jackson","doi":"10.1002/cbic.202500055","DOIUrl":"https://doi.org/10.1002/cbic.202500055","url":null,"abstract":"A cyclase-phosphotriesterase (C-PTE) from Ruegeria pomeroyi DSS-3 has recently been identified for its capacity to detoxify several organophosphate compounds. However, several aspects of this enzyme remain unexplored, such as its activity with industrial organophosphates, its molecular structure and its thermostability. In this work, we report the crystal structure of C-PTE, which was solved to 2.3 Å resolution, providing insight into the enzyme's mechanism of action, revealing a binuclear Zn2+ active site and distant similarity to other phosphotriesterases from the amidohydrolase superfamily. We show that C-PTE catalyzes the hydrolysis of the OP plasticizers triphenyl phosphate (TPhP) and tris(2- chloropropyl) phosphate (TCPP), albeit with low efficiency, but not the sterically bulkier tri-otolyl phosphate (ToTP). Finally, we show that, even though Ruegeria pomeroyi DSS-3 is not a thermophile, C-PTE exhibits remarkable thermostability and retains structure up to 90 °C. Overall, our findings advance our understanding of C-PTE, suggest that it is a good candidate for engineering owing to its thermostability and that it could contribute to bioremediation strategies to reduce the impact of pollution by industrial organophosphates.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500055"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957507","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

Balancing ROS for Enhanced Wound Healing: A Transformative Strategy. 平衡活性氧促进伤口愈合：一种变革性策略。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-13 DOI: 10.1002/cbic.202500255

Bo Chen, Zhan Ding, Yue Dai

引用次数: 0

PCFT Independent Cellular Uptake of Cyclic Cell Penetrating Peptide Conjugated Folic Acid. 环细胞穿透肽共轭叶酸的PCFT独立细胞摄取。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-13 DOI: 10.1002/cbic.202500242

Vineet Kumar Mishra, Rheal Towner, Juan Carlos Rodriguez-Lecompte, Marya Ahmed

{"title":"PCFT Independent Cellular Uptake of Cyclic Cell Penetrating Peptide Conjugated Folic Acid.","authors":"Vineet Kumar Mishra, Rheal Towner, Juan Carlos Rodriguez-Lecompte, Marya Ahmed","doi":"10.1002/cbic.202500242","DOIUrl":"https://doi.org/10.1002/cbic.202500242","url":null,"abstract":"Folic acid is an essential component of many metabolic processes, including the synthesis of nucleoproteins, purines, and pyrimidines and is a recommended supplement to lower the incidence of various disorders. Folic acid and folate loaded nanoparticles are extensively evaluated for sustained release and enhanced stability of the molecule, however malfunctioning of Proton Coupled Folate Transporters (PCFT) present on the intestinal cells, and subsequent folate deficiency remain a major issue in this context. This study provides first demonstration where cell-penetrating peptide conjugated folic acid mediate PCFT independent folic acid permeabilization and intracellular bioavailability in vitro in the intestinal cells and macrophages. Cyclic-Transactivating transcriptional activator (cTAT) folic acid conjugates are prepared by solid phase peptide synthesis and are evaluated for the cellular uptake and bioavailability in the presence and absence of PCFT inhibitors. Compared with free folic acid that showed PCFT mediated cellular uptake, cTAT-folic acid conjugates exhibited enhanced cellular uptake at all studied pH and improved intracellular bioavailability of the cargo, as was determined by dihydrofolate reductase (DHFR) assay. Folic acid and cTAT-folic acid conjugates also dampened the production of pro-inflammatory mediators in the presence of toxins in vitro in macrophage cell lines.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500242"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951597","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

Fine-Tuning Ferroptosis by Modulating GPX4 and Its Potential in Mitigating Neuronal Degeneration in Parkinson′s Disease 通过调节GPX4微调铁下垂及其减轻帕金森病神经元变性的潜力

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-12 DOI: 10.1002/cbic.202401052

Michael M. Shahid, Grace Hohman, Mohamed Eldeeb

{"title":"Fine-Tuning Ferroptosis by Modulating GPX4 and Its Potential in Mitigating Neuronal Degeneration in Parkinson′s Disease","authors":"Michael M. Shahid, Grace Hohman, Mohamed Eldeeb","doi":"10.1002/cbic.202401052","DOIUrl":"https://doi.org/10.1002/cbic.202401052","url":null,"abstract":"The increasing prevalence of neurodegenerative diseases necessitates the development of novel approaches to study, diagnose, and treat these devastating disorders. Accordingly, there is a critical need to precisely address the gap in the biochemical and physiological mechanisms that underlie neurodegenerative diseases to promote advancements in therapeutic interventions. Parkinson's Disease (PD), the second most common neurodegenerative disorder after Alzheimer's, demands further research focused on unravelling the rather intricate molecular mechanisms that drive its progression upon different cell signaling cues. While alpha-synuclein aggregation and mitochondrial dysfunction are two cellular hallmarks of the molecular pathophysiology of PD, few drugs are currently in clinical trials for treatment of PD, which warrants further studies to identify new therapeutic molecular targets. Herein, we briefly highlight some of the reported roles of ferroptosis, a modality of cell death that is driven by iron-dependent phospholipid peroxidation, and its regulation by glutathione peroxidase 4 (GPX4). We discuss the interconnectedness between lipid peroxidation and GPX4 regulation in the context of molecular pathogenesis of PD. Future studies are imperative in investigating the physiological role of ferroptosis and the translational impact of ferroptosis-specific modulators in studying PD biology.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938892","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

Cover Feature: Characterization of ActVI-ORF3 and ActVI-ORF4 as Lactonizing and Delactonizing Enzymes in Relation to Metabolic Flux in Actinorhodin Biosynthesis (ChemBioChem 9/2025) 封面专题：ActVI-ORF3和ActVI-ORF4作为内酯化酶和去乙酰化酶与放线鸟素生物合成代谢通量的关系（ChemBioChem 9/2025）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-05-12 DOI: 10.1002/cbic.202580904

Dr. Makoto Hashimoto, Dr. Kazuki Ishikawa, Yuri Fukushima, Sarina Shimazu, Mizuha Yabuzaki, Yuka Kamezawa, Dr. Takaaki Taguchi, Prof. Dr. Koji Ichinose

引用次数: 0

ChemBioChem最新文献