Benýšek, Jakub Buša, Michal Rubešová, Petra Fanfrlík, Jindřich Lepšík, Martin Brynda, Jiří Matoušková, Zuzana Bartz, Ulrike Horn, Martin Gütschow, Michael
...
Published in
Journal of enzyme inhibition and medicinal chemistry
Cathepsin K (CatK) is a target for the treatment of osteoporosis, arthritis, and bone metastasis. Peptidomimetics with a cyanohydrazide warhead represent a new class of highly potent CatK inhibitors; however, their binding mechanism is unknown. We investigated two model cyanohydrazide inhibitors with differently positioned warheads: an azadipeptide...
Douglas, Lisa E J Reihill, James A Ho, Melisa W Y Axten, Jeffrey M Campobasso, Nino Schneck, Jessica L Rendina, Alan R Wilcoxen, Keith M Martin, S Lorraine
Published in
Cell chemical biology
In cystic fibrosis (CF), excessive furin activity plays a critical role in the activation of the epithelial sodium channel (ENaC), dysregulation of which contributes to airway dehydration, ineffective mucociliary clearance (MCC), and mucus obstruction. Here, we report a highly selective, cell-permeable furin inhibitor, BOS-318, that derives selecti...
Redondo-Calvo, Francisco Javier Padín, Juan Fernando Muñoz-Rodríguez, José Ramón Serrano-Oviedo, Leticia López-Juárez, Pilar Porras Leal, María Lourdes González Gasca, Francisco Javier Rodríguez Martínez, Marta Pérez Serrano, Raúl Sánchez Cadena, Abraham
...
Published in
European journal of clinical investigation
SARS-CoV-2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two-step furin-mediated entry mechanism. Aprotinin is a broad-spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti-inflammatory properties for inhibiting the innat...
Napolitano, Valeria Dabrowska, Agnieszka Schorpp, Kenji Mourão, André Barreto-Duran, Emilia Benedyk, Malgorzata Botwina, Pawel Brandner, Stefanie Bostock, Mark Chykunova, Yuliya
...
Published in
Cell chemical biology
The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor....
ramalho, camila
Cell adhesion and migration are crucial for cancer progression and malignancy. Drugs available for the treatment of metastatic melanoma are expensive and unfit for certain patients. Therefore, there is still a need to identify new drugs that block tumor cell development. We investigated the effects of Enterolobium contortisiliquum trypsin inhibitor...
rhee;, soo-yon
Ritonavir-boosted atazanavir is an option for second-line therapy in low- and middle-income countries (LMICs). We analyzed publicly available HIV-1 protease sequences from previously PI-naïve patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 publ...
Kiyozumi, Daiji Ikawa, Masahito
Published in
Frontiers in Endocrinology
The physiological roles of proteolysis are not limited to degrading unnecessary proteins. Proteolysis plays pivotal roles in various biological processes through cleaving peptide bonds to activate and inactivate proteins including enzymes, transcription factors, and receptors. As a wide range of cellular processes is regulated by proteolysis, abnor...
Renko, Miha Zupan, Tanja Plaza, David F Schmieder, Stefanie S Perišić Nanut, Milica Kos, Janko Turk, Dušan Künzler, Markus Sabotič, Jerica
Published in
International journal of molecular sciences
We introduce a new family of fungal protease inhibitors with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, which inhibit both cysteine and aspartic proteases. Two cocaprin-encoding genes are differentially expressed in fungal tissues. One is highly transcribed in vegetative mycelium and the other in the stipes of mature fru...
Renko, Miha Zupan, Tanja Plaza, David F Schmieder, Stefanie S Perišić Nanut, Milica Kos, Janko Turk, Dušan Künzler, Markus Sabotič, Jerica
We introduce a new family of fungal protease inhibitors with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, which inhibit both cysteine and aspartic proteases. Two cocaprin-encoding genes are differentially expressed in fungal tissues. One is highly transcribed in vegetative mycelium and the other in the stipes of mature fru...
ramalho, camila
The action of proteases can be controlled by several mechanisms, including regulation through gene expression; post-translational modifications, such as glycosylation; zymogen activation; targeting specific compartments, such as lysosomes and mitochondria; and blocking proteolysis using endogenous inhibitors. Protease inhibitors are important molec...
