Article
Medicine, Research & Experimental
Lena Ostermann, Regina Maus, Jennifer Stolper, Lisanne Schutte, Konstantina Katsarou, Srinu Tumpara, Andreas Pich, Christian Mueller, Sabina Janciauskiene, Tobias Welte, Ulrich A. Maus
Summary: The study found that in AAT-deficient mice, NE can degrade lung SP-A and SP-D, affecting lung protective immunity. Treatment with human AAT or the NE-specific inhibitor Sivelestat can protect collectins from degradation and reduce bacterial loads in S. pneumoniae-infected AAT-KO mice.
Article
Agriculture, Multidisciplinary
Johan S. Perez Campos, Yaremis B. Merino-Cabrera, Javier G. Mantilla-Afanador, Graziela D. A. Lima, Samuel L. Barbosa, Camilo E. Vital, Rafael Barros, Neilier Rodrigues-Junior, Eugenio E. Oliveira, Maria G. A. Oliveira
Summary: This study characterized the protease activities in the salivary glands of the Neotropical brown stink bug and investigated the impact of insecticide resistance on these enzyme activities. The findings suggest that insecticide resistance can significantly alter the activities of proteolytic enzymes in phytosuccivorous stink bug pests.
ANNALS OF APPLIED BIOLOGY
(2021)
Article
Engineering, Biomedical
Chensi Wang, Changxuan Shao, Yuxin Fang, Jiajun Wang, Na Dong, Anshan Shan
Summary: The hybridization of SFTI-1 binding loop with linear antimicrobial peptide (AMP) sequence is confirmed to improve its protease stability. The target compound, RV3, exhibits selective membrane-lytic effects both in vitro and in vivo, and has anti-inflammatory effects when applied topically on wounded murine skin. These findings reveal a potential method for designing or optimizing AMP using natural amino acid sequences, which could facilitate the development and clinical application of peptide-based antibacterial biomaterials.
ACTA BIOMATERIALIA
(2021)
Review
Biochemistry & Molecular Biology
Noora Barzkar, Zahoor Khan, Saeid Tamadoni Jahromi, Sajjad Pourmozaffar, Mohsen Gozari, Reza Nahavandi
Summary: Marine organisms are valuable sources of enzymes and their inhibitors with great therapeutic potential, particularly serine proteases and their inhibitors showing promise in biomedical applications. The uncontrolled activity of these proteases can lead to diseases, but their actions are regulated by serine protease inhibitors to maintain physiological functions.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Alec Millner, Logan Running, Nicole Colon-Rosa, Diana S. Aga, Jonna Frasor, G. Ekin Atilla-Gokcumen
Summary: This study identifies a novel lipid regulator involved in therapy-induced senescence and suggests that ceramide kinase could be a potential target enzyme to decrease the levels of therapy-induced senescent cells.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Kevin Van Holsbeeck, Baptiste Fischer, Simon Gonzalez, Charlene Gadais, Wim Versees, Jose C. Martins, Charlotte Martin, Alexandre Wohlkoenig, Jan Steyaert, Steven Ballet
Summary: RAS proteins play a crucial role in regulating intracellular signaling networks and mutations that stabilize their active state are associated with cancer development. The study investigated the potential of developing peptide mimetics to modulate RAS signaling by mimicking the complementarity-determining region 3 (CDR3) of the regulatory guanine nucleotide exchange factor (GEF) son of sevenless 1 (SOS1). Through optimization and conformational rigidification, CDR3 mimetics with half of the maximal activation potential of Nanobody14 (Nb14) were obtained, demonstrating the feasibility of modulating protein-protein interactions through structural mimicry of a paratope.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jakov Ivkovic, Shalinee Jha, Christian Lembacher-Fadum, Johannes Puschnig, Prashant Kumar, Viktoria Reithofer, Karl Gruber, Peter Macheroux, Rolf Breinbauer
Summary: This study reports on the design, synthesis, and characterization of peptidomimetic inhibitors targeting DPP3 using a hydroxyethylene transition-state mimetic. The inhibitors mimic the VVYPW-motif of tynorphin and show efficient inhibition of DPP3 in low mu M range. Biophysical characterization confirms the unusual entropy-driven mode of binding.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Immunology
Xin Zhang, Miao Li, Layla El Moussawi, Sally Saab, Shasha Zhang, Mike A. Osta, Kristin Michel
Summary: Humoral immune responses in animals are tightly controlled by regulated proteolysis, where extracellular protease cascades activate key immune proteins and enzymes. In mosquitoes, the protease network regulates melanization reactions and affects resistance against microorganisms.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Medicine, Research & Experimental
E. Burchacka, P. Pieta, A. Lupicka-Slowik
Summary: There are four types of antifungal drugs targeting different aspects of fungi, but increasing resistance poses a challenge to treatment options. Thus, developing new drug strategies is crucial for addressing fungal diseases effectively.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Chemistry, Medicinal
Palmi Modi, Bhumi M. Shah, Shivani Patel
Summary: Caspase-1 plays a critical role in the inflammatory process by activating pro-inflammatory cytokines. Inhibiting Caspase-1 has therapeutic potential for inflammatory diseases. However, currently available drugs have limitations. Developing more effective therapeutic strategies is necessary.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Hanxi Yang, Mengyuan You, Xiaoyang Shu, Jingyao Zhen, Mengwei Zhu, Tiantian Fu, Yan Zhang, Xiangrui Jiang, Leike Zhang, Yechun Xu, Yumin Zhang, Haixia Su, Qiumeng Zhang, Jingshan Shen
Summary: A series of peptidomimetic compounds containing benzothiazolyl ketone and [2.2.1] azabicyclic ring were synthesized and evaluated for their inhibition of SARS-CoV-2 3CLpro. Compound 11j showed the best enzyme inhibition activity and exhibited significant anti-SARS-CoV-2 activity with low cytotoxicity. It displayed promising pharmacokinetic properties and could serve as a lead compound for further development of oral 3CLpro inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Katarzyna Maslowska, Ewa Witkowska, Dagmara Tymecka, Pawel Krzysztof Halik, Aleksandra Misicka, Ewa Gniazdowska
Summary: The aim of this study was to design and synthesize radioconjugates of peptide-type inhibitors for imaging and treating NRP-1-related cancers. The radiolabeling reaction showed good efficiency and the radiocompounds demonstrated satisfactory stability in solutions mimicking human body fluids. However, enzymatic degradation limited the stability of these radiocompounds in human serum.
Review
Microbiology
Ben A. Shurina, Richard C. Page
Summary: The CTX-M family of enzymes poses a significant clinical concern due to their ability to confer resistance to a wide range of antibiotics. Structural studies on CTX-M-15 in complex with various ligands provide insights into the interactions between the enzyme and inhibitors, offering opportunities for predicting interactions with potential drug candidates and developing new antibiotics and inhibitors.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jiri Dostal, Jiri Brynda, Lucie Vankova, Syeda Rehana Zia, Iva Pichova, Olga Heidingsfeld, Martin Lepsik
Summary: Pathogenic Candida albicans yeasts often cause infections in hospitals, requiring new antifungal drugs due to drug resistance. The study identified Sapp1p as a promising target in C. parapsilosis and revealed the structural determinants for subnanomolar inhibition, which could be utilized for designing potent and specific antifungal drugs.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jimin Hwang, Natalie Strange, Rami Mazraani, Matthew J. Phillips, Allan B. Gamble, Wilhelmina M. Huston, Joel D. A. Tyndall
Summary: A new series of CtHtrA inhibitors were developed by proline ring expansion and Cg-substitutions, which showed significantly improved antichlamydial activity in vitro.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Magdalena Wysocka, Anita Romanowska, Natalia Gruba, Michalina Michalska, Artur Gieldon, Adam Lesner
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Natalia Gruba, Lech Stachurski, Adam Lesner
Summary: Bladder cancer is a common cancer with high recurrence rate and poor prognosis, usually asymptomatic and requiring invasive and expensive regular re-examinations. The study used chromogenic substrates for qualitative determination of urine enzyme activity in healthy individuals and bladder cancer patients, finding proteolytic activity in cancer patients but not in healthy volunteers.
CHEMISTRY & BIODIVERSITY
(2021)
Letter
Respiratory System
Seda Seren, Lohann Derian, Irem Keles, Antoine Guillon, Adam Lesner, Loic Gonzalez, Thomas Baranek, Mustapha Si-Tahar, Sylvain Marchand-Adam, Dieter E. Jenne, Christophe Paget, Youenn Jouan, Brice Korkmaz
EUROPEAN RESPIRATORY JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Vincent Mariaule, Aicha Kriaa, Souha Soussou, Soufien Rhimi, Houda Boudaya, Juan Hernandez, Emmanuelle Maguin, Adam Lesner, Moez Rhimi
Summary: Proteolytic imbalance is often linked to diseases, especially in digestive inflammation. Serine proteases and matrix metalloproteases play crucial roles in inflammatory responses, but the imbalance between these enzymes and their inhibitors could contribute to disease pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Natalia Stach, Abdulkarim Karim, Przemyslaw Golik, Radoslaw Kitel, Katarzyna Pustelny, Natalia Gruba, Katarzyna Groborz, Urszula Jankowska, Sylwia Kedracka-Krok, Benedykt Wladyka, Marcin Drag, Adam Lesner, Grzegorz Dubin
Summary: By studying the substrate specificity and structure of SplF, it was found that the enzyme has a strict preference for long aliphatic sidechains at the P1 subsite and significant selectivity for aromatic residues at P3, with its crystal structure defining the structural basis of this substrate specificity. Comparisons with other Spl proteases suggest that the spl operon encodes a unique extracellular proteolytic system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Anita Romanowska, Katarzyna Wegrzyn, Katarzyna Bury, Emilia Sikorska, Aleksandra Gnatek, Agnieszka Piwkowska, Igor Konieczny, Adam Lesner, Magdalena Wysocka
Summary: Novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues were synthesized and their cell permeability, cytotoxicity, and DNA-binding ability were investigated in this study. The compounds showed efficient cell membrane penetration, dsDNA binding, and minimal cytotoxicity. The interaction with plasmid DNA and the length of the main chain of the compounds influenced the formation of unique nanostructures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Hela Mkaouar, Vincent Mariaule, Soufien Rhimi, Juan Hernandez, Aicha Kriaa, Amin Jablaoui, Nizar Akermi, Emmanuelle Maguin, Adam Lesner, Brice Korkmaz, Moez Rhimi
Summary: Inflammatory bowel diseases are incurable disorders with increasing prevalence and global socioeconomic impact. Gut microbiota dysbiosis and increased activity of serine proteases may play roles in the onset and maintenance of the disease, with potential therapeutic relevance of gut microbiota serpins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Paulina Kosikowska-Adamus, Emilia Sikorska, Dariusz Wyrzykowski, Aleksandra Walewska, Anna Golda, Milena Deptula, Michal Obuchowski, Adam Prahl, Michal Pikula, Adam Lesner
Summary: Antimicrobial peptides have broad-spectrum activity against microorganisms and can neutralize toxins and modulate inflammatory responses. Lipidation can enhance their antimicrobial potential and stability, but may also impact selectivity, solubility, and cytotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Natalia Gruba, Lech Stachurski, Adam Lesner
Summary: Inflammation is often linked to cancer development and progression, and late diagnosis of inflammation leading to cancer can reduce chances of successful treatment. A study using chromogenic substrates in urine samples found that proteolytic activity may be related to cancer development, particularly in bladder cancer. This research supports the broader use of urine for inflammation screening.
JOURNAL OF BIOCHEMISTRY
(2021)
Article
Cell Biology
Aicha Kriaa, Amin Jablaoui, Soufien Rhimi, Souha Soussou, Hela Mkaouar, Vincent Mariaule, Natalia Gruba, Ali Gargouri, Emmanuelle Maguin, Adam Lesner, Moez Rhimi
Summary: The study found that gut microbial protease activity may be an important contributor to IBD, and oral administration of recombinant bacteria secreting SP-1 compromises the epithelial barrier, alters the microbial community, and exacerbates colitis. This suggests that targeting gut microbial protease activity could be a promising approach for treating the disease.
Article
Biochemistry & Molecular Biology
Iga Biskupek, Adam Sieradzan, Cezary Czaplewski, Adam Liwo, Adam Lesner, Artur Gieldon
Summary: This manuscript proposes a two-stage infection mechanism of the SARS-CoV-2 virus, highlighting the crucial role of the interaction between the virus and the ACE2 receptor in the infection process, and identifies the importance of three key residues.
Review
Cell Biology
Aicha Kriaa, Vincent Mariaule, Amin Jablaoui, Soufien Rhimi, Hela Mkaouar, Juan Hernandez, Brice Korkmaz, Adam Lesner, Emmanuelle Maguin, Ali Aghdassi, Moez Rhimi
Summary: Inflammatory bowel diseases (IBDs) are a global public health problem with limited effective therapeutic options. Changes in gut microbiota composition and alterations in bile acids (BAs) have been identified as important factors in dysregulated intestinal immunity and the pathogenesis of IBDs. This review explores the interactions between BAs and gut microbiota in IBDs and discusses how the gut microbiota-BA-host axis may influence digestive inflammation.
Article
Pharmacology & Pharmacy
Wioletta Brankiewicz, Joanna Okonska, Katarzyna Serbakowska, Jan Lica, Marek Drab, Natalia Ptaszynska, Anna Legowska, Krzysztof Rolka, Piotr Szweda
Summary: This study reported five conjugates composed of fluconazole and cell penetrating or antimicrobial peptide, showing high antifungal activity, especially against fluconazole-resistant strains, with low cytotoxicity.
Article
Biochemistry & Molecular Biology
Mladena Glavas, Agata Gitlin-Domagalska, Natalia Ptaszynska, Dominika Starego, Sylwia Freza, Dawid Debowski, Aleksandra Helbik-Maciejewska, Anna Legowska, Chaim Gilon, Krzysztof Rolka
Summary: Arginine increases peptides' hydrophilicity and enables interactions with charged molecules, but its presence may reduce permeability through biological membranes. Temporary coverage of peptide charge with lipophilic, enzyme-sensitive alkoxycarbonyl groups can resolve this issue. We present a new, optimized strategy to obtain arginine building blocks with increased lipophilicity.
