We have developed a sensitive luminometric assay for determining the activity of retroviral proteases that uses proteolytic cleavage of polypeptide substrate immobilized on Ni-NTA HisSorb Strips microplates. The protease substrate derived from the Gag precursor protein of Mason-Pfizer monkey virus (M-PMV) was conjugated with horseradish peroxidase (HRP), which catalyzes oxidation of luminol in the assay. The cleavage of the substrate was monitored as a decrease in luminescent signal caused by the release of the cleavage product conjugated to HRP. Testing of a set of M-PMV protease inhibitors confirmed that this method is sufficiently sensitive and specific for high-throughput screening of retroviral protease inhibitors.
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http://dx.doi.org/10.1016/j.ab.2005.07.013 | DOI Listing |
Curr Vasc Pharmacol
January 2025
Department of Pharmacy, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Neutrophil elastase (NE), a major protease in neutrophils, is important in promoting inflammation and multiple pathological processes. While NE is released abundantly in ischemiareperfusion (I/R) injury, the intricate relationship between NE and I/R injury remains unclear. We examine several aspects of how NE is involved in I/R injury.
View Article and Find Full Text PDFFront Nutr
December 2024
Key Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen, China.
Introduction: Hyperlipidemia remains a major disease threatening global public health. The morbidity and mortality associated with cardiovascular diseases have been increasing. The inhibition of 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a key enzyme in the cholesterol synthesis pathway, can effectively reduce cholesterol levels.
View Article and Find Full Text PDFJ Immunother Precis Oncol
February 2025
Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombotic microangiopathy resulting from decreased activation of the von Willebrand factor-cleaving protease (ADAMTS13). TTP can cause organ damage and is often fatal if the appropriate treatment is not started immediately. Although primary immune TTP is the most common form of TTP, secondary immune etiologies, including complications from immune checkpoint inhibitors (ICIs), have also been reported.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Sustainable Chemistry for Metals and Molecules, Department of Chemistry, KU Leuven, Leuven 3000, Belgium.
Cruzipain (CZP) is an essential cysteine protease of , the etiological agent of Chagas disease, and a promising druggable target. To date, no CZP inhibitors have reached clinical use, with research efforts mostly hampered by insufficient potency, limited target selectivity or lack of bioactivity translation from the isolated enzyme to the parasite in cellular environments. In this study, we report the design of , a 1,2,3-triazole-based targeted covalent inhibitor with nanomolar potency (IC = 28 nM) and null inhibition of human cathepsin L.
View Article and Find Full Text PDFCurr Hypertens Rep
January 2025
Department of Pharmacy, The Second Clinical Medical College, The First Affiliated Hospital, Shenzhen People's Hospital, Jinan University, Southern University of Science and Technology), Shenzhen, China.
Purpose Of Review: To review currently existing knowledge on a new type of antihypertensive treatment, small interfering RNA (siRNA) targeting hepatic angiotensinogen.
Recent Findings: Targeting angiotensinogen synthesis in the liver with siRNA allows reaching a suppression of renin-angiotensin system (RAS) activity for up to 6 months after 1 injection. This might revolutionize antihypertensive treatment, as it could overcome non-adherence, the major reason for inadequate blood pressure control.
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