Review
Cell Biology
Jan E. Strobech, Pietro Giuriatti, Janine T. Erler
Summary: This review focuses on the role of neutrophils in regulating the extracellular matrix and how neutrophil-secreted proteases promote cancer metastasis.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Environmental Sciences
Karolina Nowak, Ewa Jablonska, Marzena Garley, Agnieszka Iwaniuk, Piotr Radziwon, Slawomir Wolczynski, Wioletta Ratajczak-Wronaa
Summary: This study investigated the estrogen-like effects and mechanism of action of commonly used parabens in human neutrophils. The results showed that parabens did not have cytotoxic effects on neutrophils, nor did they affect neutrophil functions or expression of estrogen receptors.
ENVIRONMENTAL RESEARCH
(2022)
Article
Immunology
Patrick P. Mcdonald, Franziska Graf Leifer, Jessica Basso, Dan Lasala, Dedong Li, Kuan-Ju Chen, Jimin Zhang, Walter R. Perkins, David C. Cipolla
Summary: The efficacy of the DPP-1 inhibitor brensocatib was assessed in rat and mouse models, showing significant reduction in bone marrow NSP levels and improvement in disease score. In the mouse model, brensocatib even demonstrated similar efficacy to anti-TNF antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Max E. Huber, Lara Toy, Maximilian F. Schmidt, Hannah Vogt, Julian Budzinski, Martin F. J. Wiefhoff, Nicole Merten, Evi Kostenis, Dorothee Weikert, Matthias Schiedel
Summary: By developing a chemical biology toolbox targeting CCR9, we identified a new intracellular CCR9 antagonist and the first PROTAC targeting IABS of GPCRs, providing a novel approach to modulate GPCR activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Wang Wan, Lianggang Zeng, Wenhan Jin, Xinxin Chen, Di Shen, Yanan Huang, Mengdie Wang, Yulong Bai, Haochen Lyu, Xuepeng Dong, Zhenming Gao, Lei Wang, Xiaojing Liu, Yu Liu
Summary: A new crystallization-induced emission fluorophore was developed to quantitatively investigate the polarity of aggregated proteins, providing insights into protein status based on changes in solvent polarity; The probe can be used for live cell quantification of aggregated protein polarity, revealing heterogeneity within cellular aggregates and potentially correlating to their biochemical properties and pathogenicity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Jian Yang, Rafal J. Mendowicz, Steven H. L. Verhelst
Summary: Activity-based probes (ABPs) are valuable chemical tools for profiling enzymes, particularly proteases. Alkyne-substituted benzoxazin-4-ones can covalently inhibit serine proteases and be used for labeling and identifying various serine proteases, offering easily synthesizable tools for their profiling.
Review
Chemistry, Multidisciplinary
Daan Sondag, Stijn Verhoeven, Dennis W. P. M. Lowik, Mark van Geffen, Cornelis van't Veer, Waander L. van Heerde, Thomas J. Boltje, Floris P. J. T. Rutjes
Summary: The blood coagulation cascade is a complex physiological process that involves multiple enzymes, cofactors, and substrates, leading to clot formation. Serine proteases play a crucial role, and abnormalities in their activity can result in life-threatening bleeding disorders and thrombosis. This review summarizes the important proteases involved in blood coagulation and fibrinolysis, their recognition and hydrolysis of endogenous peptide sequences, and synthetic peptide probes for measuring their activity. The information in this review can contribute to the development of novel anticoagulant therapies and specific substrates for point-of-care diagnosis of coagulation pathologies.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Chemistry, Multidisciplinary
Daan Sondag, Stijn Verhoeven, Dennis W. P. M. Lowik, Mark van Geffen, Cornelis van't Veer, Waander L. van Heerde, Thomas J. Boltje, Floris P. J. T. Rutjes
Summary: The blood coagulation cascade is a complex process involving multiple enzymes, cofactors, and substrates, and its dysregulation can lead to bleeding disorders and thrombosis. This review summarizes the key proteases involved in blood clot formation and fibrinolysis, their recognition and hydrolysis of endogenous peptide sequences, and the use of synthetic peptide probes for measuring their activity. The information provided in this review can contribute to the development of novel anticoagulant therapies and specific substrates for point-of-care diagnosis of coagulation pathologies.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Veronika E. Reut, Stanislav O. Kozlov, Igor Kudryavtsev, Natalya A. Grudinina, Valeria A. Kostevich, Nikolay P. Gorbunov, Daria Grigorieva, Julia A. Kalvinkovskaya, Sergey B. Bushuk, Elena Yu Varfolomeeva, Natalia D. Fedorova, Irina Gorudko, Oleg M. Panasenko, Vadim B. Vasilyev, Alexey Sokolov
Summary: This paper introduces a fluorescent probe called Celestine Blue B (CB), which can be used for HOCl detection in living cells and for assaying the chlorinating activity of MPO. The probe shows remarkable selectivity and sensitivity, and has a rapid response to HOCl. It can also detect endogenous HOCl and reactive halogenated species using various techniques.
Review
Chemistry, Multidisciplinary
Paulina Kasperkiewicz
Summary: Proteases catalyze the hydrolysis of peptide bonds, mediating signaling in numerous biological processes. Serine proteases, accounting for 40% of all proteases, are crucial enzymes in both normal and disease-related functions. Studying serine proteases requires specific reagents for detection and imaging, with peptidyl activity-based probes being extensively researched for this purpose.
FRONTIERS IN CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Timo Burster, Fabian Gaertner, Uwe Knippschild, Anuar Zhanapiya
Summary: Uncontrolled proteolytic activity of proteases can lead to various human diseases, and activity-based probes (ABPs) are essential tools for detecting and regulating this activity. The use of ABPs allows for interference with uncontrolled proteolytic activity of proteases, offering potential therapeutic benefits.
FRONTIERS IN CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Sylwia Modrzycka, Sonia Kolt, Stephanie G. Polderdijk, Ty E. Adams, Stanislaw Potoczek, James A. Huntington, Paulina Kasperkiewicz, Marcin Drag
Summary: Activated protein C, thrombin, and factor Xa are important factors in blood coagulation and play significant roles in various diseases. The development of selective chemical tools to study their individual activities is crucial in understanding their functions in different conditions.
Review
Biochemistry & Molecular Biology
Natalia Cwilichowska, Karolina W. Swiderska, Agnieszka Dobrzyn, Marcin Drag, Marcin Poreba
Summary: Proteases are enzymes that hydrolyze peptide bonds in proteins and peptides, controlling biological processes. Disturbance of the delicate balance of proteases can lead to the development of various diseases. Understanding the role of proteases in pathological physiology has led to the development of therapeutic inhibitors and chemical probes. The identification and optimization of protease substrates and inhibitors have provided opportunities for therapeutic and diagnostic applications.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Varsha Ashok Walvekar, Karthik Ramesh, Chacko Jobichen, Muthu Kannan, J. Sivaraman, R. Manjunatha Kini, Yu Keung Mok
Summary: The specificity of Kazal-type protease inhibitors is determined by the sequence of the reactive-site loop. The crystal structure of Aedes aegypti trypsin inhibitor with mu-plasmin reveals differences in reactivities compared to other Kazal-type inhibitors. The scaffold instability of AaTI affects its ability to inhibit plasmin.
Article
Biochemistry & Molecular Biology
Nadine Anna Schilling, Hubert Kalbacher, Timo Burster
Summary: The novel SARS-CoV-2 variants exhibit increased turnover rate and additional cleavage sites at the necessary positions for priming the Spike protein. The presence of specific proteolytic sites facilitates viral entry into target cells through furin and TMPRSS2-mediated cleavage. Neutrophils, in response to infection, release serine proteases that may be exploited by the virus for cell entry.
Article
Neurosciences
Neda Sadeghi, Filippo Arrigoni, Maria Grazia D'Angelo, Cibu Thomas, M. Okan Irfanoglu, Elizabeth B. Hutchinson, Amritha Nayak, Pooja Modi, Maria Teresa Bassi, Carlo Pierpaoli
HUMAN BRAIN MAPPING
(2018)
Article
Biochemistry & Molecular Biology
Katarzyna Groborz, Sonia Kolt, Paulina Kasperkiewicz, Marcin Drag
Article
Biochemistry & Molecular Biology
Brett M. Babin, Paulina Kasperkiewicz, Tomasz Janiszewski, Euna Yoo, Marcin Drag, Matthew Bogyo
ACS CHEMICAL BIOLOGY
(2019)
Article
Chemistry, Medicinal
Sonia Kolt, Tomasz Janiszewski, Dion Kaiserman, Sylwia Modrzycka, Scott J. Snipas, Guy Salvesen, Marcin Drag, Phillip Bird, Paulina Kasperkiewicz
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Paulina Kasperkiewicz, Anne Hempel, Tomasz Janiszewski, Sonia Kolt, Scott J. Snipas, Marcin Drag, Guy S. Salvesen
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Oncology
Stephen Sakuma, Marcela Raices, Joana Borlido, Valeria Guglielmi, Ethan Y. S. Zhu, Maximiliano A. D'Angelo
Summary: Reducing nuclear pore complex (NPC) numbers in cancer cells induces cell death, prevents tumor growth, and results in tumor regression, while normal cells undergo a reversible cell-cycle arrest in response to inhibition of NPC assembly. These findings highlight the potential of targeting NPC formation as a novel pathway in cancer treatment.
Review
Developmental Biology
Valeria Guglielmi, Stephen Sakuma, Maximiliano A. D'Angelo
Article
Immunology
Alex Marki, Konrad Buscher, Cristina Lorenzini, Matthew Meyer, Ryosuke Saigusa, Zhichao Fan, Yi-Ting Yeh, Nadine Hartmann, Jennifer M. Dan, William B. Kiosses, Gregory J. Golden, Rajee Ganesan, Holger Winkels, Marco Orecchioni, Sara McArdle, Zbigniew Mikulski, Yoav Altman, Jack Bui, Mitchell Kronenberg, Shu Chien, Jeffrey D. Esko, Victor Nizet, David Smalley, Johannes Roth, Klaus Ley
Summary: ENDS are a new class of submicron bloodborne particles formed by rolling neutrophils on the vessel wall, releasing S100A8-S100A9 complex in the vessel lumen, possibly associated with inflammation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Li-En Hsieh, John Sidney, Jane C. Burns, David L. Boyle, Gary S. Firestein, Yoav Altman, Alessandro Sette, Alessandra Franco
Summary: The study described a population of human regulatory T cells (Treg) activated by IgG(+) B cells presenting peptides of the Fc region via processing of surface IgG. Functionally, these Treg cells inhibit proinflammatory responses by naive T cells and exhibit similar specificities in healthy donors and patients with rheumatoid arthritis. The findings suggest that Fc peptides processed by dendritic cells stimulate Treg expansion, impacting immune regulation in patients with rheumatoid arthritis.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kamila Wala, Wojciech Szlasa, Natalia Sauer, Paulina Kasperkiewicz-Wasilewska, Anna Szewczyk, Jolanta Saczko, Nina Rembialkowska, Julita Kulbacka, Dagmara Baczynska
Summary: This study evaluated the anticancer effect of 6-gingerol and found that it can be used in combination with paclitaxel to enhance the cytotoxic effect on breast cancer cells. The results showed that 6-gingerol induced transcription of TP53 and Bax genes, while paclitaxel mainly induced transcription of TP53.
Article
Multidisciplinary Sciences
Wojciech Szlasa, Olga Michel, Natalia Sauer, Vitalij Novickij, Damian Lewandowski, Paulina Kasperkiewicz, Mounir Tarek, Jolanta Saczko, Julita Kulbacka
Summary: This study investigates the effects of nanosecond pulsed electric fields (nsPEF) on pancreatic cancer cells and their mechanisms of action. It reveals that nsPEF treatment leads to the release of microvesicles, enhanced electropermeabilization, and cell shrinkage. It also shows that nsPEF treatment reduces tumor spheroid size and proposes a mechanism involving cell membrane surface tension and actin fiber organization.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Medicinal
Sylwia Modrzycka, Sonia Kolt, Ty E. Adams, Stanislaw Potoczek, James A. Huntington, Paulina Kasperkiewicz, Marcin Drag
Summary: Anticoagulation therapy is commonly used to treat thrombotic disorders, but it comes with the risk of bleeding. Research shows that factor XI plays a role in thrombosis, and inhibiting factor XIa can reduce the bleeding risk associated with anticoagulation therapy. Using libraries of natural and unnatural amino acids, researchers developed chemical tools to study factor XIa activity and identified selective inhibitors. These tools, such as activity-based probes, can be used to further investigate the role of factor XIa in biological samples.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Sylwia Modrzycka, Sonia Kolt, Stephanie G. Polderdijk, Ty E. Adams, Stanislaw Potoczek, James A. Huntington, Paulina Kasperkiewicz, Marcin Drag
Summary: Activated protein C, thrombin, and factor Xa are important factors in blood coagulation and play significant roles in various diseases. The development of selective chemical tools to study their individual activities is crucial in understanding their functions in different conditions.