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http://dx.doi.org/10.1002/cbic.200700279 | DOI Listing |
Angew Chem Int Ed Engl
September 2025
State Key Laboratory of Chemo and Biosensing, School of Biomedical Sciences, Hunan University, Changsha, 410082, China.
Activity-based ubiquitin probes (Ub-ABPs) are powerful tools for studying the functional landscape of deubiquitinases (DUBs). While most existing Ub probes have focused on examining the native state of DUBs, oxidative stress, especially in cancer and inflammatory contexts, can oxidize the catalytic cysteine of DUBs, significantly altering their activity. Here, we developed three novel ubiquitin-based activity probes (Ub-ABPs) to selectively trap the sulfenylated form of deubiquitinases (DUB-SOH).
View Article and Find Full Text PDFCell Chem Biol
September 2025
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China; Centre for Oncology and Im
RhoA is a key cancer driver and potential colorectal cancer (CRC) therapy target but remains undrugged clinically. Using activity-based protein profiling (ABPP) and mass spectrometry (MS), we identified CL16, a covalent inhibitor targeting the unique Cys16 on RhoA subfamily, which confers high specificity over other Rho family proteins. Cys16 is adjacent to the nucleotide-binding pocket and switch regions, which are critical for RhoA function.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2025
College of Chemistry and Molecular Sciences, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430072, P.R. China.
Peptide-based biosensors are widely used for in vitro detection of protease activity but often suffer from the limited sensitivity, poor accuracy, and incompatibility with point-of-care testing (POCT) devices. Herein, we developed a versatile deoxyribozyme (DNAzyme)-amplified protease-sensing (DP) platform that integrates the positively charged oligopeptides with a negatively charged DNAzyme biocatalyst for highly-sensitive protease detection. The system leverages the electrostatic peptide-DNAzyme interactions to inhibit DNAzyme catalytic activity, which is reactivated upon the protease-triggered peptide hydrolysis, thus enabling an efficient signal amplification via the successive cleavage of DNAzyme substrate.
View Article and Find Full Text PDFInt J Eat Disord
September 2025
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Objective: Converging evidence from neuroimaging studies and genome-wide association study (GWAS) suggests the involvement of prefrontal cortex (PFC) and striatum dysfunction in the pathophysiology of anorexia nervosa (AN). However, identifying the causal role of circuit-specific genes in the development of the AN-like phenotype remains challenging and requires the combination of novel molecular tools and preclinical models.
Methods: We used the activity-based anorexia (ABA) rat model in combination with a novel viral-based translating ribosome affinity purification (TRAP) technique to identify transcriptional differences within a specific neural pathway that we have previously demonstrated to mediate pathological weight loss in ABA rats (i.
J Biol Chem
September 2025
Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pharmacology, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA. Electronic address:
Mevalonate is a precursor for essential metabolites, such as isoprenoids and sterols. Its synthesis starts with HMGCS1 producing HMG-CoA, which is then converted to mevalonate by HMGCR, a target of statins. Cancer cells often upregulate enzymes in the mevalonate pathway (MVP) to meet their metabolic demands, leading to the development of inhibitors targeting several enzymes in this pathway.
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