ChemBioChem最新文献_第5页

Front Cover: ω-Hydroxyacid Dehydrogenases From Clostridium viride: Iron-Containing Biocatalysts With Biotechnological Potential (ChemBioChem 17/2026) 封面：从芽孢杆菌的羟基脱氢酶：具有生物技术潜力的含铁生物催化剂（ChemBioChem 17/2026）

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-14 DOI: 10.1002/cbic.70551

Tarik Begic, Julia Hill, Jan L. Stitzel, Lukas Knauer, Volker Schünemann, Markus Räschle, Berta M. Martins, Antonio J. Pierik

引用次数: 0

A Novel SXXLF Motif in the FXR N-Terminal Domain Mediates Coregulator and Interdomain Interactions FXR n端结构域中一个新的SXXLF基序介导共调控子和结构域间相互作用。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-10 DOI: 10.1002/cbic.202500967

Priscilla Villalona, Thilini Pulahinge, Tracy Yu, Jordan Wenning, Sabab Hasan Khan, Crawford Joseph Frisbie, Jill Magafas, Addison Barbe, C. Denise Okafor

{"title":"A Novel SXXLF Motif in the FXR N-Terminal Domain Mediates Coregulator and Interdomain Interactions","authors":"Priscilla Villalona, Thilini Pulahinge, Tracy Yu, Jordan Wenning, Sabab Hasan Khan, Crawford Joseph Frisbie, Jill Magafas, Addison Barbe, C. Denise Okafor","doi":"10.1002/cbic.202500967","DOIUrl":"10.1002/cbic.202500967","url":null,"abstract":"The nuclear receptor (NR) superfamily is comprised of ligand-regulated transcription factors that contain an intrinsically disordered domain at the amino-terminal end, known as the N-terminal domain (NTD). While this poorly conserved domain is known to possess ligand-independent activation function (AF-1), few NTD functions are conserved between NRs. Identified roles in other receptors include androgen receptor (AR), estrogen receptor (ER), and mineralocorticoid receptor (MR). Here, we aim to define the function of the NTD of the farnesoid X receptor (FXR), a crucial regulator of lipid and bile acid metabolism. We show that the NTD engages in interdomain contact with other FXR domains. We also observe that the NTD interacts directly with coregulator proteins. Using mutagenesis, mammalian two-hybrid assays, mammalian one-hybrid assay, and molecular dynamics (MD) simulations, we identify and validate a novel SXXLF motif in the NTD which mediates interactions with both coregulators and the ligand binding domain. Mutation of the motif induces large changes in conformational and allosteric coupling in FXR. Our study identifies a new nuclear receptor-interacting motif that modulates the transcriptional activity of FXR.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928587","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

A De Novo Peptide That Induces Axonal Growth Through TrkB Activation 通过TrkB激活诱导轴突生长的新生肽。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-10 DOI: 10.1002/cbic.70517

Rumit Maini, Kota Tamada, Kunihiro Fukuda, Toru Takumi, Hiroaki Suga

{"title":"A De Novo Peptide That Induces Axonal Growth Through TrkB Activation","authors":"Rumit Maini, Kota Tamada, Kunihiro Fukuda, Toru Takumi, Hiroaki Suga","doi":"10.1002/cbic.70517","DOIUrl":"10.1002/cbic.70517","url":null,"abstract":"Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), are key regulators of neuronal survival and synaptic plasticity. Impaired BDNF–TrkB signaling is strongly implicated in neurodegenerative and neuropsychiatric disorders, including Alzheimer's disease and major depressive disorder. However, the clinical use of BDNF is limited by poor pharmacokinetics and low tissue stability, highlighting the need for alternative TrkB agonists. Many previously reported agonists have shown inconsistent or indirect TrkB activation, raising concerns about their mechanism of action. In this study, we employed the random nonstandard peptides integrated discovery (RaPID) system to identify de novo macrocyclic peptide ligands that bind the extracellular domain of TrkB with high affinity and selectivity. One of the peptides was turned into a dimeric peptide, diTrbL3, which induced TrkB autophosphorylation and activated canonical downstream pathways, including ERK1/2 and AKT, without detectable cross-activation of other receptor tyrosine kinases. Functionally, diTrbL3 promoted axonal elongation and upregulated activity-dependent immediate early genes in primary hippocampal neurons. These findings establish diTrbL3 as a potent de novo TrkB agonist and highlight RaPID-derived macrocyclic peptides as a promising class of BDNF mimetics for targeting TrkB-dependent signaling in neurological disease.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70517","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928507","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

N8-Modified Quino[4,3,2-Kl]acridines as Promising Antimalarial G-Quadruplex Ligands n8修饰的喹诺[4,3,2- kl]吖啶烷作为抗疟疾g -四联配体的前景

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-10 DOI: 10.1002/cbic.70516

Steve Saulnier, Marco Antônio G. B. Gomes, Mariam Salim, Maxime Guichonnet, Michel Nguyen, Laure Vendier, Flore Nardella, Jean-Michel Augereau, Dennis Gomez, Anne Robert, Françoise Benoit-Vical

{"title":"N8-Modified Quino[4,3,2-Kl]acridines as Promising Antimalarial G-Quadruplex Ligands","authors":"Steve Saulnier, Marco Antônio G. B. Gomes, Mariam Salim, Maxime Guichonnet, Michel Nguyen, Laure Vendier, Flore Nardella, Jean-Michel Augereau, Dennis Gomez, Anne Robert, Françoise Benoit-Vical","doi":"10.1002/cbic.70516","DOIUrl":"10.1002/cbic.70516","url":null,"abstract":"To face the increasing multidrug resistance of the malaria parasite Plasmodium falciparum, the development of new compounds that act in novel ways is urgent. G-quadruplexes (G4), Guanine-rich secondary structures of DNA and RNA sequences, have an essential role in cell survival and cell metabolism regulation, including in Plasmodium. We have recently demonstrated that the G-quadruplex ligand RHPS4, an acridine derivative, displays strong antiplasmodial activity by disrupting P. falciparum through G4 stabilization, leading to parasite death. Based on this original mode of action, we propose here a series of new RHPS4 analogues. These derivatives were then tested against P. falciparum and on human cells to evaluate their selectivity index. They exhibited IC50 values ranging from 70 nM to up to 10 µM with cationic analogues more active than neutral ones. Their ability to interact and stabilize G-quadruplex DNA structures was also evaluated. Among all RHPS4 analogues, the compound 8b (N8-ethyl) exhibited the best activity (70 nM), a high selectivity index (143), and a significant capacity to stabilize the G4 structures.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70516","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928580","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

MMP-2 Responsive Functional Bladder Acellular Matrix Scaffold Combined With Urine Derived Stem Cells for Bladder Nerve Regeneration MMP-2反应功能膀胱脱细胞基质支架联合尿源干细胞用于膀胱神经再生。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-08 DOI: 10.1002/cbic.70500

Hao Xia, Xiaoya Wang, Wei Chen

{"title":"MMP-2 Responsive Functional Bladder Acellular Matrix Scaffold Combined With Urine Derived Stem Cells for Bladder Nerve Regeneration","authors":"Hao Xia, Xiaoya Wang, Wei Chen","doi":"10.1002/cbic.70500","DOIUrl":"10.1002/cbic.70500","url":null,"abstract":"The inadequate nerve networks in regenerated bladders remain a significant challenge in bladder tissue engineering. Our previous studies have demonstrated that incorporating basic fibroblast growth factor (bFGF) and urine-derived stem cells (USCs) into bladder acellular matrix (BAM) enhances bladder repair. While these approaches have shown promising results in regenerating bladder epithelium and smooth muscle, the outcomes of neural regeneration are still not satisfactory. Therefore, this study introduces the 1–14aa sequence from the NGF polypeptide (NMP), a small molecule NGF peptidomimetic, which could improve neural regeneration in the body. Utilizing the tissue inhibitors of metalloproteinases (TIMP) that is cleaved by MMP-2 to design an MMP-2 responsive NMP delivery system, which could control the release of NMP according to the amount of MMP-2 in the local microenvironment. By chemical cross-linking, NMP-TIMP and bFGF were conjugated with BAM seeded with USCs to compose BAM/USCs/bFGF/NMP-TIMP functional biomaterial. Using a rat bladder reconstruction model, the functional biomaterial significantly enhanced the regeneration of endothelial cells, capillaries, smooth muscle cells, nerve fibers, and the bladder functions. In summary, the BAM/USCs/bFGF/NMP-TIMP functional biomaterial may offer a promising strategy for tissue-engineered bladder by promoting bladder regeneration, especially the regeneration of bladder nerves.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904784","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 Small Molecule Substrate Mimic to Inhibit Bacterial Hsp70 Chaperone Function 抑制细菌Hsp70伴侣功能的小分子底物模拟物。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-04 DOI: 10.1002/cbic.70518

Tulsi Upadhyay, Reshma Kumari, Yogesh M. Gangarde, Upasana S. Potteth, Rishij Roychowdhury, Anirban Das, Deepanshi Saxena, Rahul Maitra, Sidharth Chopra, Ishu Saraogi

{"title":"A Small Molecule Substrate Mimic to Inhibit Bacterial Hsp70 Chaperone Function","authors":"Tulsi Upadhyay, Reshma Kumari, Yogesh M. Gangarde, Upasana S. Potteth, Rishij Roychowdhury, Anirban Das, Deepanshi Saxena, Rahul Maitra, Sidharth Chopra, Ishu Saraogi","doi":"10.1002/cbic.70518","DOIUrl":"10.1002/cbic.70518","url":null,"abstract":"Given the rapid spread of antibiotic resistance worldwide, it is imperative to develop new strategies against pathogenic bacteria. Here, we report a small-molecule inhibitor of bacterial heat shock protein 70 (Hsp70), called DnaK, a central component of the bacterial protein chaperone network. Screening of an in-house pyridylamide-based peptidomimetic library identified M7 as an inhibitor of DnaK ATPase and substrate refolding activity with intrinsic fluorescence properties. Mechanistic studies revealed that M7 likely engages the substrate-binding pocket of DnaK. Treatment of bacterial cells with M7 led to the accumulation of σ-32, without affecting protein translation, consistent with impaired DnaK function. Microscopy images of Escherichia coli AS19 cells treated with M7 revealed filamentous growth, a phenotypic defect consistent with compromised DnaK function. Moreover, M7 effectively inhibited the growth of E. coli AS19 and some Gram-positive bacteria, including Staphylococcus aureus and Bacillus cereus. These findings highlight a promising class of peptidomimetic DnaK inhibitors as potential antibacterial agents, as well as a chemical biology tool to interrogate the broader network of chaperone-mediated protein folding.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890505","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

Unnatural C6-Substituted d-Galactosides as Attenuated Substrates of Glycosyl Hydrolases 非天然c6 -取代d-半乳糖作为糖基水解酶的减毒底物

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70524

Andrey Yu. Plodukhin, Karel Hernández, Suada Demirovic, Taiwo Ogunmilade, Brandon Q. Mercado, Meghan Kennedy, Alfredo Angeles-Boza, Antoni Planas, Mark W. Peczuh

引用次数: 0

Tripled-Stranded Antisense Oligonucleotide for Biomarker-Activated Suppression of Essential Genes 生物标志物激活抑制必需基因的三链反义寡核苷酸

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70521

Valeriia S. Drozd, Lilia Tafran, Nikolay V. Zaramenskih, Yulia A. Panova, Zain Hussein, Daria S. Rybalko, Dmitry M. Kolpashchikov, Ahmed A. Eldeeb

{"title":"Tripled-Stranded Antisense Oligonucleotide for Biomarker-Activated Suppression of Essential Genes","authors":"Valeriia S. Drozd, Lilia Tafran, Nikolay V. Zaramenskih, Yulia A. Panova, Zain Hussein, Daria S. Rybalko, Dmitry M. Kolpashchikov, Ahmed A. Eldeeb","doi":"10.1002/cbic.70521","DOIUrl":"https://doi.org/10.1002/cbic.70521","url":null,"abstract":"Conditional activation of antisense oligonucleotides (ASOs) is a promising strategy for selective suppression of cancer cells without affecting normal cells. In this study, we developed a tripled-stranded ASO (tsASO) that is rendered inactive through complexation with two additional oligonucleotides. The key innovation is the use of partial overlap between the parent ASO and the biomarker sequence, combined with toehold-mediated strand displacement, enabling precise conditional activation. The tsASO effectively triggered RNase H-mediated degradation of DYNC1I2 and DARS1 RNAs exclusively in the presence of the ERBB2 sequence. In cell-free systems, the tsASO demonstrated high cleavage efficiency (up to 81%), comparable to the parent ASO efficiency, with minimal background activity in the absence of the biomarker sequence, validating the concept at the molecular level. However, in cells using lipid-based transfection, the tsASO exhibited nonspecific cytotoxicity that did not correlate with biomarker presence or target gene expression. Detailed analysis showed no clear support for known sequence-driven toxicity mechanisms (CpG/TLR9, G-quadruplexes) in the nonimmune cell lines, suggesting that the primary limitation is intracellular delivery rather than the tsASO design. Future work should focus on optimizing delivery platforms to achieve controlled cellular uptake and biomarker-dependent release, unlocking the therapeutic potential of this conditional gene silencing approach.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860053","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

Single-Residue Substitution of Opicalcin1 Enhances Cellular Uptake but Reduces Ca2+-Release Activity Opicalcin1单残基取代增强细胞摄取但降低Ca2+释放活性

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70522

Shumin Wang, Xiaoyu Hua, Xiaofen Ma, Lianbo Wang, Jianguo Wang, Hao Liu, Fei Nie, Yangfei Zhao, Qiuming Zhou, Héctor H. Valdivia, Liang Xiao, Jinming Wang

{"title":"Single-Residue Substitution of Opicalcin1 Enhances Cellular Uptake but Reduces Ca2+-Release Activity","authors":"Shumin Wang, Xiaoyu Hua, Xiaofen Ma, Lianbo Wang, Jianguo Wang, Hao Liu, Fei Nie, Yangfei Zhao, Qiuming Zhou, Héctor H. Valdivia, Liang Xiao, Jinming Wang","doi":"10.1002/cbic.70522","DOIUrl":"https://doi.org/10.1002/cbic.70522","url":null,"abstract":"The Calcin family comprises scorpion venom-derived peptides with cell-penetrating activity and reported modulatory effects on RyR-associated Ca2+ signaling. OpiCa1 differs from its homolog OpiCa2 at residue 26, making this position a candidate site for examining structure–activity relationships related to cellular uptake and Ca2+-release activity. To assess the contribution of residue 26, we generated two OpiCa1 variants, T26R and T26K by replacing Thr26 with the basic residues arginine and lysine. We compared these variants with parental OpiCa1 using in silico modeling, fluorescence-based uptake assays, cytotoxicity assessment, and Ca2+ imaging. Among the tested variants, T26R showed significantly enhanced cellular uptake compared with parental OpiCa1 and exhibited no detectable cytotoxicity at 10–60 µM under the tested conditions. In silico analyses suggested possible changes in the predicted interaction mode of T26R near the RyR S6 region. Consistent with these computational observations, cellular functional assays revealed that T26R, despite its superior uptake, concurrently attenuated Ca2+-release activity. These findings suggest that residue 26 contributes to the cellular uptake and Ca2+-release activity of OpiCa1, while further experimental studies are required to define its direct interaction with RyRs.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860048","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

Proton Transport as a Missing Design Variable in Immobilized Enzyme Catalysis 固定化酶催化中缺失的质子输运设计变量

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70519

Marek Wiśniewski

{"title":"Proton Transport as a Missing Design Variable in Immobilized Enzyme Catalysis","authors":"Marek Wiśniewski","doi":"10.1002/cbic.70519","DOIUrl":"https://doi.org/10.1002/cbic.70519","url":null,"abstract":"Carbonic anhydrase is among the fastest known enzymes, yet its performance after immobilization remains difficult to rationalize. Conventional immobilization design emphasizes stability, enzyme loading, and mass transfer while largely neglecting proton transport. In soluble carbonic anhydrase, proton transfer can limit catalytic turnover under defined pH and buffer conditions. We propose that immobilization may introduce an additional, condition-dependent resistance at the enzyme–support interface. Surface chemistry and wettability influence interfacial water organization, potentially altering hydrogen-bond dynamics and proton mobility. Strongly hydrophobic interfaces may disrupt hydration continuity, whereas strongly water-binding surfaces may restrict water reorientation and exchange, suggesting a system-dependent intermediate wettability window. We further introduce the concept of a surface proton antenna, in which appropriately positioned proton-relay groups could extend the enzyme’s intrinsic pathway through interfacial water. This hypothesis must be distinguished from effects of enzyme orientation, conformational changes, substrate diffusion, confinement, buffer capacity, local pH, and product accumulation. Using carbonic anhydrase as a mechanistic model, this perspective reframes immobilization supports as potentially active components of proton-coupled catalytic interfaces and identifies interfacial proton transport as a testable design variable for CO2 conversion and other biocatalytic processes.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860051","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