Article
Biochemistry & Molecular Biology
Tanaya Bagga, S. N. Loh, J. Sivaraman, Srihari Shankar
Summary: This study reports the crystal structure of human neutrophil elastase (hNE) in complex with a peptide inhibitor derived from ecotin (ET). The study found that short linear peptides and circular amide backbone-linked peptides had inefficient inhibition of hNE. Structural insights point to a preferred amino acid sequence and the potential benefits of a scaffold for optimal binding and function of the peptide inhibitor.
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
Alessandra Biasiolo, Michele Sandre, Stefania Ferro, Santina Quarta, Mariagrazia Ruvoletto, Gianmarco Villano, Cristian Turato, Maria Guido, Oriano Marin, Patrizia Pontisso
Summary: This study aimed to generate antibodies against different SerpinB3 epitopes to better understand their biological role. Five exposed epitopes were identified and corresponding synthetic peptides were used for rabbit immunization. Anti-P#2 and anti-P#4 antibodies could recognize both SerpinB3 and SerpinB4, while anti-P#5 antibody showed the greatest specific reactivity for human SerpinB3 and could recognize SerpinB3 at the nuclear level.
Article
Chemistry, Medicinal
Daniels Jelisejevs, Anna Lina Bula, Linda Kinena
Summary: The study investigates /q- and y-lactams as electrophilic warheads for covalently targeting the Mpro active site at Cys145. The highest inhibitory activity was achieved using a pyrazolidinone warhead attached to the targeting dipeptide. Notably, the synergy between the warhead and the targeting dipeptide is crucial for the successful inhibition of Mpro.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Stefan Gerhardy, Mark Ultsch, Wanjian Tang, Evan Green, Jeffrey K. Holden, Wei Li, Alberto Estevez, Chris Arthur, Irene Tom, Alexis Rohou, Daniel Kirchhofer
Summary: This study describes the allosteric inhibition mechanism of the clinical Fab fragment on HTRA1, a genetic risk factor associated with geographic atrophy. The binding of Fab to LoopA of HTRA1 locks it into an inactive state, inhibiting its catalytic activity. The study also demonstrates that the allosteric inhibition mechanism can be transferred to other proteases in the HTRA family by grafting the LoopA epitope. The findings provide insights into the inhibition mechanism of the clinical Fab and highlight the critical role of LoopA in the activity of HTRA family proteases.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Philip Maximilian Knaff, Patrick Mueller, Christian Kersten, Lukas Wettstein, Jan Muench, Katharina Landfester, Volker Mailaender
Summary: The study developed high-affinity tetrapeptidic inhibitors using a combinatorial methodology, which can selectively inhibit the overexpression of hepsin in tumor progression.
Article
Immunology
Yannan Ji, Tengfei Lu, Zhen Zou, Yanhong Wang
Summary: Researchers have discovered that a clip-domain serine protease, CLIPB9, mediates the cleavage activation of PPO3, and that CLIPA14 acts as a cofactor for PPO3 activation in the mosquito Aedes aegypti. Co-silencing of CLIPB9 and CLIPA14 genes increases the sensitivity of adult mosquitoes to fungal infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Exequiel O. J. Porta, Jaime A. Isern, Karunakaran Kalesh, Patrick G. Steel
Summary: In this study, a new therapeutic target for the treatment of leishmaniasis was discovered using an activity-based protein profiling strategy to investigate serine proteases (SPs) in Leishmania parasites. Significant differences in the expression levels of active Leishmania serine hydrolases (SHs) were observed throughout the parasite's life cycle and between different species. Two targetable SPs were identified in Leishmania mexicana using quantitative proteomic mass spectrometry. The results of this study provide templates for the discovery of new drugs for the treatment of leishmaniasis.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Abdur Rauf, Anees Ahmed Khalil, Ahmed Olatunde, Muneeb Khan, Sirajudheen Anwar, Ahmed Alafnan, Kannan R. R. Rengasamy
Summary: Marine habitats are rich in diverse life forms that offer potential sources of novel bioactive compounds, including protease inhibitors with significant applications in pharmaceutical, nutraceutical, and cosmeceutical industries. Despite extensive research on protease inhibitors, many compounds have not advanced to clinical trials, highlighting the ongoing need for exploring new sources for their development.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Li Zhou, In Ho Jeong, Songyi Xue, Menglin Xue, Lei Wang, Sihao Li, Ruochuan Liu, Geon Ho Jeong, Xiaoyu Wang, Jianfeng Cai, Jun Yin, Bo Huang
Summary: The enzymatic cascades for ubiquitin transfer play a key role in regulating cellular processes and are the focus of drug development for cancer and neurodegenerative diseases. In this study, we used peptide mimetics to inhibit the interaction between E1 and E2, and identified two effective inhibitors for blocking ubiquitin transfer. Our findings suggest that targeting protein-protein interactions involving the N-terminal helix of E2 could be a promising strategy for designing inhibitors against protein ubiquitination pathways.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Sitanshu S. Singh, George Mattheolabakis, Xin Gu, Sita Withers, Achyut Dahal, Seetharama Jois
Summary: This study developed grafted peptides to inhibit protein-protein interactions of EGFR and HER2 in NSCLC, with SFTI-G5 showing promising antiproliferative activity. In vivo experiments demonstrated that SFTI-G5 could inhibit tumor growth and reduce EGFR dimerization, indicating its potential as a novel dual inhibitor in NSCLC.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Andreza Alves Belo, Dayane L. Naves de Souza, Marcella Nunes De Melo-Braga, Leticia Lopes de Souza, Denis A. Molina Molina, Patricia D. Vaz de Melo, Martin R. Larsen, Clara Guerra-Duarte, Carlos Chavez-Olortegui
Summary: This study successfully generated a neutralizing antibody against Bothrops snake venom in Brazil, specifically targeting its coagulant activity. The use of monoclonal antibodies for immunoaffinity chromatography proved to be an effective technique for purifying bioactive toxins from the venom.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Multidisciplinary
Deborah Grifagni, Vito Calderone, Stefano Giuntini, Francesca Cantini, Marco Fragai, Lucia Banci
Summary: This study elucidated the structural basis of ionic zinc binding to the SARS-CoV-2 main protease using X-ray crystallography. The zinc binding affinity and its ability to inhibit the main protease were investigated, providing a solid foundation for the design of potent and selective metal-conjugated inhibitors.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biology
Lukas Wettstein, Philip Maximilian Knaff, Christian Kersten, Patrick Mueller, Tatjana Weil, Carina Conzelmann, Janis A. Mueller, Maximilian Brueckner, Markus Hoffmann, Stefan Poehlmann, Tanja Schirmeister, Katharina Landfester, Jan Muench, Volker Mailaender
Summary: This study describes the development and characterization of peptidomimetic inhibitors of TMPRSS2, which primes the Spike protein of SARS-CoV-2. The inhibitors are shown to prevent SARS-CoV-2 infection in cells as efficiently as camostat mesylate.
COMMUNICATIONS BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Nina Zupanic, Jernej Pocic, Adrijana Leonardi, Jernej Sribar, Dusan Kordis, Igor Krizaj
Summary: Serine proteases play a crucial role in physiology and pathology. The discovery of nonenzymatic functions in pseudo serine proteases (SPHs) has expanded our understanding of the role of these proteins. SPHs have been found to be important in reproduction, embryonic development, immune response, host defense, and hemostasis. Investigating the interaction between SPs and SPHs can uncover new physiological functions and aid in the development of innovative medical approaches.
