Article
Chemistry, Medicinal
Adela Jilkova, Petra Rubesova, Jindrich Fanfrlik, Pavla Fajtova, Pavlina Rezacova, Jiri Brynda, Martin Lepsik, Helena Mertlikova-Kaiserova, Cory D. Emal, Adam R. Renslo, William R. Roush, Martin Horn, Conor R. Caffrey, Michael Mares
Summary: This study identified potent inhibitors of Schistosoma mansoni cathepsin B1, a validated drug target for schistosomiasis treatment. The inhibitors showed high bioactivity against the pathogen, selectivity for the target enzyme, and favorable metabolic stability. These results provide structural insights for the rational design of next-generation inhibitors for potential schistosomiasis drugs.
ACS INFECTIOUS DISEASES
(2021)
Article
Biotechnology & Applied Microbiology
Alyaa Farid
Summary: In many tropical regions, schistosomiasis is a major parasitic disease that causes significant morbidity and mortality, second only to malaria. Diagnostic methods include microscopy, radiography, and serology. Proteases have been investigated as targets for immunological or chemotherapeutic anti-Schistosoma agents due to their importance in the parasitic life cycle.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Susanna Haapanen, Andrea Angeli, Martti Tolvanen, Reza Zolfaghari Emameh, Claudiu T. T. Supuran, Seppo Parkkila
Summary: This study reports the sequence enhancement, production, catalytic activity, and inhibition results of the beta-class carbonic anhydrase SmaBCA from intestinal parasite Schistosoma mansoni. The recombinant SmaBCA showed significant catalytic activity on CO2 hydration in vitro. Several sulphonamide inhibitors, including clinically used ones, exhibited submicromolar or nanomolar inhibitory effects on SmaBCA. The results suggest SmaBCA as a novel target for drug development against schistosomiasis.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Parasitology
Rosangela Lima de Freitas Galvao, Gdayllon Cavalcante Meneses, Marta Cristhiany Cunha Pinheiro, Alice Maria Costa Martins, Elizabeth De Francesco Daher, Fernando Schemelzer Moraes Bezerra
Summary: This study aimed to investigate kidney damage in patients infected with S. mansoni through urinary biomarkers of kidney injury and its association with parasite load. The results showed that urinary VEGF levels were significantly higher in patients infected with S. mansoni, regardless of the parasite load, indicating increased signs of podocyte damage.
Article
Biochemistry & Molecular Biology
Aya Al-Naseri, Samar Al-Absi, Noha Mahana, Hatem Tallima, Rashika El Ridi
Summary: In this study, it was discovered that Schistosoma mansoni cathepsin B1 (SmCB1), helminth cathepsins of the L family (e.g., SmCL3), and papain can significantly reduce challenge worm burden and egg viability. However, when used in combination, they do not provide additional protection. The study also found that different immunogens have opposing effects on egg quantity and vitality.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2022)
Article
Chemistry, Medicinal
W. U. Lu-Yang, M. A. Yang-Min, L. E. Shan, Wang Tian-Hao, Feng Yi
Summary: The study utilized Topomer CoMFA to construct a 3D-QSAR model for 39 peptidyl vinyl sulfone cysteine protease inhibitors, demonstrating good estimation stability and prediction capability. The screening resulted in 22 new molecules with predicted activity higher than the template molecules. Molecular docking revealed extensive interactions between inhibitors and active site residues.
LETTERS IN DRUG DESIGN & DISCOVERY
(2021)
Article
Parasitology
Simone Parn, Gabriela Lewis, Matty Knight
Summary: This study identified the upregulation of the CA gene in susceptible B. glabrata snails during infection, and the inhibitory effect of aspirin on its expression. The findings suggest that this model system could provide new insights into the role of CA in cancer cell metastasis and proliferation.
EXPERIMENTAL PARASITOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jakub Benysek, Michal Busa, Petra Rubesova, Jindrich Fanfrlik, Martin Lepsik, Jiri Brynda, Zuzana Matouskova, Ulrike Bartz, Martin Horn, Michael Gutschow, Michael Mares
Summary: This study investigates the binding mechanism of two model cyanohydrazide inhibitors with Cathepsin K (CatK) and reveals that the extraordinary potency of Gu2602 is favored by its conformational flexibility. The study also demonstrates the effectiveness of cyanohydrazides in targeting mature CatK in osteosarcoma cells and inhibiting the autoactivation of CatK. These findings provide important structural insights for the design of cyanohydrazide inhibitors as potential drugs.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Carina Lemke, Adela Jilkova, Dominic Ferber, Annett Braune, Anja On, Patrick Johe, Alena Zikova, Tanja Schirmeister, Michael Mares, Martin Horn, Michael Gutschow
Summary: We developed a bimodal rhodesain probe that can detect and quantify rhodesain with high sensitivity, and used it for inhibitor screening. This probe provides a new tool for studying Trypanosoma pathobiochemistry and antitrypanosomal drug discovery.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Michal Busa, Zuzana Matouskova, Pavla Bartosova-Sojkova, Petr Pachl, Pavlina Rezacova, Ramon Marc Eichenberger, Peter Deplazes, Martin Horn, Sasa Stefanic, Michael Mares
Summary: Fasciolosis is a parasitic disease caused by the liver fluke Fasciola hepatica and has become an emerging human disease. The protein FhCyLS-2 from F. hepatica is a member of the cystatin superfamily and has characteristics of both intracellular stefins and secreted true cystatins. It acts as a broad specificity inhibitor of cysteine cathepsins, playing a dual role in the regulation of exogenous and endogenous proteolysis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Physical
J. Rezac, J. J. P. Stewart
Summary: Semiempirical quantum-mechanical computational methods are widely used in the study of biomolecular systems, but their ability to accurately describe protein structures is not well understood. In this study, the structures of 19 proteins were optimized using several semiempirical QM methods, and compared to high-resolution crystal structures. Some methods showed good agreement with the experimental structures, while others introduced artificial close contacts that could be improved through reparameterization.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Jingjing Lin, Irena Selicharova, Katarina Mitrova, Benjamin Fabre, Vijay Madhav Miriyala, Martin Lepsik, Jiri Jiracek, Maria Soledad Garre Hernandez
Summary: Insulin is a crucial hormone for regulating energy balance in the body. Designing insulin dimers may be an effective strategy for modulating receptor activation or altering specificity towards insulin receptor isoforms.
JOURNAL OF PEPTIDE SCIENCE
(2023)
Article
Chemistry, Physical
Jindrich Fanfrlik, Jiri Brynda, Michael Kugler, Martin Lepsik, Klara Pospisilova, Josef Holub, Drahomir Hnyk, Jan Nekvinda, Bohumir Gruner, Pavlina Rezacova
Summary: This paper provides the first example of B-H...pi hydrogen bonding in a protein-ligand complex through high-resolution X-ray crystallography and quantum-chemical calculations. The study demonstrates that the B-H...pi interaction is stabilized by dispersion, followed by electrostatics. It also shows that the similar C-H...pi interaction is twice as strong, with a slightly smaller contribution of dispersion and a slightly higher contribution of electrostatics. Such insights will facilitate the rational design of future protein ligands, controlling these types of non-covalent interactions.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Parasitology
Kristyna Peterkova, Jiri Vorel, Jana Ilgova, Pavel Ostasov, Pavla Fajtova, Lukas Konecny, Marta Chanova, Martin Kasny, Martin Horn, Jan Dvorak
Summary: This study investigates the proteases and inhibitors expressed by Schistosoma mansoni eggs using comparative transcriptomics. The findings suggest that these molecules may play important roles in egg tissue migration, stimulation of angiogenesis, and interaction with host blood and immunity.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2023)
Article
Multidisciplinary Sciences
Marcela Pavova, Paul Eduardo Reyes-Gutierrez, Jaroslav Kozak, Juraj Dobias, Yevgen Yurenko, Martin Lepsik, Filip Teply, Jan Weber
Summary: G-quadruplexes, which are nucleic acids containing quartets of guanines, play a role in regulating gene transcription. Helquat-based compounds have been identified as a new class of anti-HIV-1 inhibitors that can stabilize G-quadruplexes in the HIV-1 long-terminal repeat sequence. This discovery can contribute to the rational design of inhibitors targeting G-quadruplexes in HIV-1.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Vanessa Porkolab, Martin Lepsik, Stefania Ordanini, Alexander St John, Aline Le Roy, Michel Thepaut, Emanuele Paci, Christine Ebel, Anna Bernardi, Franck Fieschi
Summary: DC-SIGN functions as the coreceptor for SARSCoV-2 virus, and a glycomimetic ligand called Polyman26 inhibits DC-SIGN-dependent trans-infection. By designing dendrimer constructs that can engage two binding sites of the tetrameric DC-SIGN simultaneously, the researchers were able to achieve nanomolar affinity. This study opens up possibilities for developing new virus attachment blockers for different C-type lectin receptors.
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Miroslav Kuba, Petro Khoroshyy, Martin Lepsik, Erika Kuzmova, David Kodr, Tomas Kraus, Michal Hocek
Summary: A modified dC(TO)TP was designed and synthesized with a thiazole orange moiety tethered via an oligoethylene glycol linker. It could be incorporated into DNA by DNA polymerases in vitro and live cells. The fluorescence lifetime of the thiazole orange moiety differed significantly when dC(TO)TP was incorporated into DNA compared to its non-incorporated forms. By delivering dC(TO)TP into live U-2 OS cells using a synthetic nucleoside triphosphate transporter, it enabled real-time detection and monitoring of cells actively synthesizing DNA from the beginning.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Willi Keller, Menyhart B. Sarosi, Jindrich Fanfrlik, Michal Straka, Josef Holub, Michael L. McKee, Drahomir Hnyk
Summary: A new type of monocationic borane and heteroborane clusters have been obtained through a one-pot reaction with N-heterocyclic carbenes, resulting in the formation of closo-dicationic octahedral phosphahexaborane and pnictogenahexaboranes of the same shape. The existence of these species in solution has been confirmed by DFT/ZORA/NMR approach, and the computed electrostatic potentials have revealed the charge delocalization within the octahedral shapes.
Article
Chemistry, Inorganic & Nuclear
Willi Keller, Matthias Hofmann, Hubert Wadepohl, Markus Enders, Jindrich Fanfrlik, Drahomir Hnyk
Summary: This study discovered a new compound SeB9Cl9 through the vacuum co-pyrolysis reaction and characterized its molecular structure and chemical properties using various techniques. The research also demonstrated the exceptional stability of octahedral, bicapped square-antiprismatic, and icosahedral closo motifs in the SeBnCln family.
DALTON TRANSACTIONS
(2023)