Mechanisms of the amide bond hydrolysis catalyzed by proteolytic enzymes have been analyzed using mainly our own experimental data. The rationale for the efficiency and specificity of proteinases has been proposed that relates these features to the state of the substrate in the productive enzyme-substrate complex.
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RSC Med Chem
December 2024
State Key Laboratory of Biocatalysis and Enzyme Engineering, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, School of Life Sciences, Hubei University Wuhan 430062 China
Despite the success of endocrine therapies in treating ER-positive breast cancer, the development of resistance remains a significant challenge. Estrogen receptor targeting proteolysis-targeting chimeras (ER PROTACs) offer a unique approach by harnessing the ubiquitin-proteasome system to degrade ER, potentially bypassing resistance mechanisms. In this review, we present the drug design, efficacy and early clinical trials of these ER PROTACs.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Dermatology & Venerology, West China Hospital, Sichuan University, Chengdu 610041, China.
Molecular mechanisms of chaperone-mediated autophagy (CMA) constitute essential regulatory elements in cellular homeostasis, encompassing protein quality control, metabolic regulation, cellular signaling cascades, and immunological functions. Perturbations in CMA functionality have been causally associated with various pathological conditions, including neurodegenerative pathologies and neoplastic diseases. Recent advances in targeted protein degradation (TPD) methodologies have demonstrated that engineered degraders incorporating KFERQ-like motifs can facilitate lysosomal translocation and subsequent proteolysis of noncanonical substrates, offering novel therapeutic interventions for both oncological and neurodegenerative disorders.
View Article and Find Full Text PDFTheranostics
January 2025
Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.
Mutations in the synaptic protein MAM domain containing glycosylphosphatidylinositol anchor 2 (MDGA2) have been associated with autism spectrum disorder (ASD). Therefore, elucidating the regulatory mechanisms of MDGA2 can help develop effective treatments for ASD. Liquid chromatography-tandem mass spectrometry was carried out to identify proteins interacting with the extracellular domain of RPS23RG1 and with MDGA2, followed by co-immunoprecipitation assays to confirm protein-protein interactions.
View Article and Find Full Text PDFEcotoxicol Environ Saf
January 2025
Key laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China; SCU-CUHK Joint Laboratory for Reproductive Medicine, Zebrafish Research Platform, West China Second University Hospital, Children's Medicine Key Laboratory of Sichuan Province, Sichuan University/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610000, PR China. Electronic address:
Noise pollution has become a significant concern for human health, yet its effects on early embryonic development remain underexplored. Specifically, data on the impact of sine wave noise on newly fertilized embryos is limited. This study aimed to address this gap by using zebrafish embryos at the 1-cell stage as a model to assess the toxicity of sine waves, following OECD Test No.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Hematology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Background: Targeting exportin1 (XPO1) with Selinexor (SEL) is a promising therapeutic strategy for patients with multiple myeloma (MM). However, intrinsic and acquired drug resistance constitute great challenges. SEL has been reported to promote the degradation of XPO1 protein in tumor cells.
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