ChemBioChem最新文献

Detecting the Undetectable: Advances in Methods for Identifying Small Tau Aggregates in Neurodegenerative Diseases.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-17 DOI: 10.1002/cbic.202400877

David Klenerman, Dorothea Böken, Yunzhao Wu, Ziwei Zhang

引用次数: 0

Drug Discovery Approaches to Target E3 Ligases.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-17 DOI: 10.1002/cbic.202400656

Alejandra Rodríguez-Gimeno, Carles Galdeano

引用次数: 0

Proton Occupancies in Histidine Side Chains of Carbonic Anhydrase II by Neutron Crystallography and NMR - Differences, Similarities and Opportunities.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-17 DOI: 10.1002/cbic.202400930

Suzanne Zoë Fisher, Heiner N Raum, Ulrich Weininger

{"title":"Proton Occupancies in Histidine Side Chains of Carbonic Anhydrase II by Neutron Crystallography and NMR - Differences, Similarities and Opportunities.","authors":"Suzanne Zoë Fisher, Heiner N Raum, Ulrich Weininger","doi":"10.1002/cbic.202400930","DOIUrl":"https://doi.org/10.1002/cbic.202400930","url":null,"abstract":"Histidine is a key amino-acid residues in proteins that can exist in three different protonation states: two different neutral tautomeric forms and a protonated, positively charged one. It can act as both donor and acceptor of hydrogen bonds, coordinate metal ions, and engage in acid/base catalysis. Human Carbonic Anhydrase II (HCA II) is a pivotal enzyme catalyzing the reversible hydration of carbon dioxide. It contains 12 histidine residues: six surface exposed, two buried, three active site zinc ion ligands, and one is a proton shuttle. Comparing results from NMR spectroscopy with previously determined neutron protein crystal structures enabled a side-by-side investigation of the proton occupancies and preferred tautomeric states of the histidine residues in HCA II. Buried and zinc coordinating histidines remain in one neutral tautomeric state across the entire pH range studied, as validated by both methods. In contrast, solvent-exposed histidines display high variability in proton occupancies. While the data were overall remarkably consistent between methods, some discrepancies were observed, shedding light on the limitations of each technique. Therefore, combining these methods with full awareness of the advantages and drawbacks of each, provides insights into the dynamic protonation landscape of HCA II histidines, crucial for elucidating enzyme catalytic mechanisms.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400930"},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833276","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

177Lu Radiolabeled Polydopamine Decorated with Fibroblast Activation Protein Inhibitor for Locoregional Treatment of Glioma.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-17 DOI: 10.1002/cbic.202400579

Yadong Wang, Long Qiu, Tianzhen Ye, Fuyuan Tan, Jie Lyu, Feize Li, Zhizhong Sun, Yuanyou Yang, Jinsong Zhang, Ning Liu, Jiali Liao

引用次数: 0

Vanadium Complexes for Mitochondria-Targeted Photodynamic Therapy.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-17 DOI: 10.1002/cbic.202400901

Md Kausar Raza, Arun Kumar

引用次数: 0

Derivative Technologies of Expansion Microscopy and Applications in Biomedicine.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-16 DOI: 10.1002/cbic.202400795

Dongling Jia, Minhui Cui, Adeleh Divsalar, Tawfik A Khattab, Salhah D Al-Qahtani, Edwin Cheung, Xianting Ding

{"title":"Derivative Technologies of Expansion Microscopy and Applications in Biomedicine.","authors":"Dongling Jia, Minhui Cui, Adeleh Divsalar, Tawfik A Khattab, Salhah D Al-Qahtani, Edwin Cheung, Xianting Ding","doi":"10.1002/cbic.202400795","DOIUrl":"https://doi.org/10.1002/cbic.202400795","url":null,"abstract":"Expansion microscopy (ExM) is an innovative super-resolution imaging technique that utilizes physical expansion to magnify biological samples, facilitating the visualization of cellular structures that are challenging to observe using traditional optical microscopes. The fundamental principle of ExM revolves around employing a specialized hydrogel to uniformly expand biological samples, thereby achieving super-resolution imaging under conventional optical imaging conditions. This technology finds application not only in various biological samples such as cells and tissue sections, but also enables super-resolution imaging of large biological molecules including proteins, nucleic acids, and metabolite molecules. In recent years, numerous researchers have delved into ExM, resulting in the continuous development of a range of derivative technologies that optimize experimental protocols and broaden practical application fields. This article presents a comprehensive review of these derivative technologies, highlighting the utilization of ExM for anchoring nucleic acids, proteins, and other biological molecules, as well as its applications in biomedicine. Furthermore, this review offers insights into the future development prospects of ExM technology.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400795"},"PeriodicalIF":2.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833273","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

Synthesis and preliminary evaluation of Tanshinone Mimic conjugates for mechanism of action studies. 用于作用机制研究的丹参酮模拟共轭物的合成和初步评估。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-16 DOI: 10.1002/cbic.202400917

Giulia Assoni, Ágata Sofia Assunção Carreira, Matteo Tomiello, Pierfausto Seneci, Alessandro Provenzani, Daniela Arosio

{"title":"Synthesis and preliminary evaluation of Tanshinone Mimic conjugates for mechanism of action studies.","authors":"Giulia Assoni, Ágata Sofia Assunção Carreira, Matteo Tomiello, Pierfausto Seneci, Alessandro Provenzani, Daniela Arosio","doi":"10.1002/cbic.202400917","DOIUrl":"https://doi.org/10.1002/cbic.202400917","url":null,"abstract":"Human antigen R (HuR) is an RNA binding protein (RBP) belonging to the ELAV (Embryonic Lethal Abnormal Vision) family, which stabilizes mRNAs and regulates the expression of multiple genes. Its altered expression or localization is related to pathological features such as cancer or inflammation. Dihydrotanshinone I (DHTS I) is a naturally occurring, tetracyclic ortho-quinone inhibitor of the HuR-mRNA interaction. Our earlier efforts led to the identification of a synthetic Tanshinone Mimic (TM) 2 with improved affinity for HuR. Here we report five new TM probes 3-5 bearing a detection-promoting moiety (either photo affinity probe - PAP or biotin) as a para-substituent on the phenyl-sulphonamide for mechanism of action (MoA) studies. Biological and biochemical assays were used to characterize the novel TM conjugates 3-5. They showed similar toxic activity in HuR-expressing triple-negative breast cancer MDA-MB-231 cells, with micromolar IC50s. REMSAs revealed that photoactivatable groups (4a and 4b), but not biotin (5a and 5b), prevented conjugates' ability to disrupt rHuR-RNA complexes. Further biochemical studies confirmed that biotinylated probes, in particular 5a, can be used to isolate rM1M2 from solutions, taking advantage of streptavidin-coated magnetic beads, thus being the most promising HuR inhibitor to be used for further MoA studies in cell lysates.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400917"},"PeriodicalIF":2.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826713","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

Formation of Poly-L-Lysine-Porphyrin Derivative Complex Exhibiting Diminished Dark Toxicity in Aqueous Solutions and High Photodynamic Activity. 形成聚-L-赖氨酸-卟啉衍生物复合物，在水溶液中的暗毒性减弱，光动力活性高。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-15 DOI: 10.1002/cbic.202400926

Yusuke Egashira, Nanami Kono, Naoki Tarutani, Kiyofumi Katagiri, Shodai Hino, Keita Yamana, Riku Kawasaki, Atsushi Ikeda

引用次数: 0

Multiphoton Excited Fluorescence Imaging over Metal-Organic Frameworks.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-15 DOI: 10.1002/cbic.202400782

Qingwei Huo, Tong Meng, Xin Lu, Dandan Li

引用次数: 0

Unraveling the molecular basis for G-quadruplex-binders to ALS/FTD-associated G4C2 repeats of the C9orf72 gene.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-12-13 DOI: 10.1002/cbic.202400974

Luisa D'Anna, Darren Wragg, Daniela Mauro, Simona Rubino, Alessio Terenzi, Giampaolo Barone, Sophie Thomas, Angela Casini, Riccardo Bonsignore, Angelo Spinello

{"title":"Unraveling the molecular basis for G-quadruplex-binders to ALS/FTD-associated G4C2 repeats of the C9orf72 gene.","authors":"Luisa D'Anna, Darren Wragg, Daniela Mauro, Simona Rubino, Alessio Terenzi, Giampaolo Barone, Sophie Thomas, Angela Casini, Riccardo Bonsignore, Angelo Spinello","doi":"10.1002/cbic.202400974","DOIUrl":"https://doi.org/10.1002/cbic.202400974","url":null,"abstract":"The most recurrent familial cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the presence of an abnormal number of intronic GGGGCC (G4C2) repetitions in the C9orf72 gene, which has been proposed to drive ALS/FTD pathogenesis. Recently, it has been shown that such G4C2 repetitions can fold into G-quadruplex (G4) secondary structures. These G4s have been selectively stabilized by small-molecule binders, furnishing proof of principle that targeting these non-canonical nucleic acid sequences represents a novel and effective therapeutic strategy to tackle neurodegenerative disorders. However, precise information on the mechanism of action of these compounds is still lacking. Here, by performing in silico investigations, we unraveled the molecular basis for the selectivity of a series of known structurally related C9orf72 G4-binders. Moreover, we investigated the binding properties of a strong and selective metal-based G4 stabilizer, the AuI bis-N-heterocyclic carbene (NHC) complex - Au(TMX)2 - showing that it moderately stabilizes G4C2 G4 RNA by Förster resonance energy transfer (FRET) DNA melting assays. Using metadynamics (metaD) simulations, the Au(TMX)2 binding mode and the associated free-energy landscape were also evaluated. This information paves the way for developing improved compounds to tackle ALS/FTD neurodegenerative disorders.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400974"},"PeriodicalIF":2.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816760","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