Article
Chemistry, Analytical
Yufan Fan, Tiantian Zhang, Yunqing Song, Zhipei Sang, Hairong Zeng, Peiqi Liu, Ping Wang, Guangbo Ge
Summary: This study developed a highly specific near-infrared substrate for human carboxylesterase 2A (hCES2A) and established a high-throughput biochemical assay for screening potent inhibitors. Furthermore, the substrate showed high imaging resolution for imaging hCES2A in living systems.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Matthias Koch, Thomas Enzlein, Shu-Yu Chen, Dieter Petit, Sam Lismont, Martin Zacharias, Carsten Hopf, Lucia Chavez-Gutierrez
Summary: This study explores the mechanism that controls the processing of the amyloid precursor protein (APP) by gamma-secretases, which is crucial in determining the length of amyloid-beta (A beta) peptides and their role in Alzheimer's disease (AD) pathogenesis. The researchers found that polar interactions established by the APPC99 ectodomain (ECD) play a key role in regulating the cleavage of APP by gamma-secretases. Increasing the hydrophobicity of APPC99-ECD attenuates substrate-driven product release and rescues the effects of Alzheimer's disease-associated pathogenic gamma-secretase and APP variants on A beta length. Furthermore, the study reveals that APPC99-ECD facilitates the production of longer A beta peptides caused by certain gamma-secretase inhibitors. These findings highlight the importance of the APPC99-ECD in regulating gamma-secretase activity and suggest it as a potential target for developing compounds that can selectively promote APP processing by these enzymes.
Article
Biochemistry & Molecular Biology
Katja F. Hellendahl, Maryke Fehlau, Sebastian Hans, Peter Neubauer, Anke Kurreck
Summary: The study introduces a luciferase-based assay for the detection of NK activity, which was validated in a 96-well plate format. The high-throughput assay showed comparable results to HPLC analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Chao Wang, Zhenhao Tian, Yifei Wang, Ming Zhang, Baojing Zhang, Lei Feng, Xiangge Tian, Huilian Huang, Jingnan Cui, Xiaochi Ma
Summary: A fluorescent probe activated by an enzyme was designed to detect bacterial gamma-GT activity, allowing real-time monitoring and in vitro imaging of various bacteria. Additionally, a high-throughput screening system was established to identify novel inhibitors of bacterial gamma-GT from natural compounds and herbal medicines library. Baicalein, myricetin and amaronol A from herbal medicines were confirmed as bacterial gamma-GT inhibitors for the first time.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Biochemistry & Molecular Biology
Salvatore Santamaria, Frederic Buemi, Elisa Nuti, Doretta Cuffaro, Elena De Vita, Tiziano Tuccinardi, Armando Rossello, Steven Howell, Shahid Mehmood, Ambrosius P. Snijders, Rens de Groot
Summary: ADAMTS-7 extracellular protease is considered a potential therapeutic target for atherosclerosis and coronary artery disease. A novel fluorescence substrate, ATS7FP7, was developed for high-throughput screening of ADAMTS-7 inhibitors, which may accelerate translational studies for treating cardiovascular diseases.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Meng-Ru Sun, Li-Lin Song, Hui-Zhen Wei, Jin-Hui Shi, Bei Zhao, Tian Tian, Yun-Qing Song, Zhen-Hao Tian, Guang-Hui Zhu, Guang-Bo Ge
Summary: A rational substrate design strategy was used to construct a highly specific and high-affinity fluorogenic substrate for real-time sensing and functional imaging of hNotum in complex biological systems. The substrate displayed good performance for sensing hNotum with rapid response, ultrahigh sensitivity, excellent specificity, and high binding affinity. It was also used for high-throughput screening of hNotum inhibitors and an efficacious activator of Wnt signaling cascade was identified.
SENSORS AND ACTUATORS B-CHEMICAL
(2023)
Article
Biochemistry & Molecular Biology
Dieter Petit, Manuel Hitzenberger, Matthias Koch, Sam Lismont, Katarzyna Marta Zoltowska, Thomas Enzlein, Carsten Hopf, Martin Zacharias, Lucia Chavez-Gutierrez
Summary: This study investigates the interactions between an imidazole-based GSM and its target gamma-secretase-APP, and reveals that a part of the modulator interacts with a binding site on gamma-secretase, triggering rearrangements and stabilizing enzyme-substrate interactions.
Article
Immunology
Xiaojing Wen, Li Zhang, Shan Zhao, Qiang Liu, Wenyi Guan, Jiajing Wu, Qiwei Zhang, Hongling Wen, Weijin Huang
Summary: The study found that cardamomin has good anti-human adenovirus 5 (HAdV5) activity both in vitro and in vivo, and can protect tissues from virus-induced damage. This research established a method for high-throughput screening of anti-HAdV5 drugs and demonstrated cardamomin as a potential new treatment for patients infected with adenoviruses.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sandeep Bhosale, Matthew C. Deen, Cameron Proceviat, Andrew Hettle, Dana K. Winter, Jacob Brockerman, Marina Levene, Andrew J. Bennet, Claude Spino, Alisdair B. Boraston, David J. Vocadlo
Summary: Trimming of host glycans is a common mechanism used by both commensal and pathogenic microflora for colonization. Streptococcus pneumoniae, an opportunistic Gram-positive bacterium, employs glycan processing enzymes and the exo-mannosidase SpGH92 as a virulence factor. The synthesis of a fluorogenic disaccharide substrate and the identification of a potential inhibitor for SpGH92 are reported.
ACS CHEMICAL BIOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Daniel R. Dries, Gang Yu
Summary: Research showed that gamma-secretase is a potential therapeutic target for Alzheimer's disease, and provided new opportunities for treatment.
Article
Biochemistry & Molecular Biology
Yanli Sun, Haibo Lu, Xueyu Fang, Senhao Xiao, Feng Yang, Yantao Chen, Hongbo Wang, Xiaopeng Li, Jing Lu, Hua Lin, Cheng Luo, Kehao Zhao, Shijie Chen
Summary: Tumor suppressor p53-binding protein 1 (53BP1) plays a crucial role in DNA Damage Repair pathways and its dysregulation is associated with various diseases including cancer. Recent studies have identified a novel and effective 53BP1-TTD inhibitor DP308, disrupting the binding between 53BP1 and H4K20me2 peptide, showing promise as a potential tool for further optimization of biological functions and gene editing therapies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jiachen Wen, Dan Liu, Linxiang Zhao
Summary: Gamma-secretase is a large transmembrane protein complex consisting of four distinct units, which has garnered attention for its role in intramembrane proteolysis. The recent discovery of its atomic structure through cryo-EM has enhanced our understanding of its physiological functions and facilitated the development of novel molecules targeting gamma-secretase. This review focuses on the latest progress of gamma-secretase inhibitors and modulators in clinical and preclinical stages, as well as their potential applications in various biological indications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Joanna E. Luo, Yue-Ming Li
Summary: Alzheimer's disease is a common neurodegenerative disorder associated with the accumulation of A beta peptides. γ-secretase, the enzyme responsible for generating A beta peptides, has been a challenging drug target due to its complex structure and function. However, the development of γ-secretase modulators has opened up new possibilities for Alzheimer's disease treatment.
CELL AND BIOSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Congkuan Song, Jinjin Zhang, Chenzhen Xu, Minglang Gao, Ning Li, Qing Geng
Summary: This article discusses the potential and problems of gamma-secretase and its inhibitors in cancer treatment, introducing gamma-secretase as a multi-substrate enzyme and its important role in cellular activities. The failure of current GSIs in clinical trials may be attributed to various factors.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Sophia D. Staerz, Erika M. Lisabeth, Evert Njomen, Thomas S. Dexheimer, Richard R. Neubig, Jetze J. Tepe
Summary: The balance between protein degradation and synthesis, proteostasis, is key for proper cellular function. The majority of intracellular protein degradation occurs through the ubiquitin-proteasome system, with pathways targeting unfolded proteins playing an important role. Dysregulation of proteolysis can lead to the accumulation of intrinsically disordered proteins (IDPs), contributing to various diseases. Enhancing the activity of the 20S proteasome using small molecules, such as erlotinib, has shown potential in combating IDP accumulation.
