Article
Multidisciplinary Sciences
Elina Lidumniece, Chrislaine Withers-Martinez, Fiona Hackett, Christine R. Collins, Abigail J. Perrin, Konstantinos Koussis, Claudine Bisson, Michael J. Blackman, Aigars Jirgensons
Summary: Malaria is a devastating infectious disease causing over 400,000 deaths annually. Researchers have developed substrate-based peptidic boronic acids that inhibit a parasite protease called SUB1, preventing parasite replication through egress and potentially serving as a new class of antimalarial drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Nikos Kuehl, Johannes Lang, Mila M. Leuthold, Christian D. Klein
Summary: This study synthesized novel benzoxaborole inhibitors and evaluated their biological activity against the proteases of SARS-CoV-2 and dengue viruses. The most active compound showed strong inhibition against SARS-CoV-2 and significant inhibitory effects against dengue virus replication in cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Amiram Sananes, Itay Cohen, Irit Allon, Oshrit Ben-David, Raghda Abu Shareb, Ksenia M. Yegodayev, David Stepensky, Moshe Elkabets, Niv Papo
Summary: Targeted therapies for prostate, breast, and ovarian cancers are based on their activity against primary tumors rather than their anti-metastatic activity. There is an urgent need for new agents targeting the metastatic process. Mesotrypsin and KLK6 are attractive putative targets for therapeutic intervention.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yasel Guerra, Vinicio Armijos-Jaramillo, Tirso Pons, Eduardo Tejera, Colin Berry
Summary: The Kunitz-Soybean Trypsin Inhibitor (Kunitz-STI) family is a large family of proteins with most of its members being protease inhibitors. This study analyzed the crystallographic structures of Kunitz-STI inhibitors to characterize the structural features and locations of serine protease-binding loops. The findings suggest a relationship between the conformation of these loops, the inhibition mechanism, and the plant source of the inhibitors. This research challenges the perception that all Kunitz-STI inhibitors are canonical and will aid in the identification and design of multifunctional proteins.
Article
Chemistry, Medicinal
Zenichi Ikeda, Taku Kamei, Yusuke Sasaki, Matthew Reynolds, Nozomu Sakai, Masato Yoshikawa, Michiko Tawada, Nao Morishita, Douglas R. Dougan, Chien-Hung Chen, Irena Levin, Hua Zou, Masako Kuno, Naoto Arimura, Yusuke Kikukawa, Mitsuyo Kondo, Kimio Tohyama, Kenjiro Sato
Summary: We explored a novel series of non-amidine-based C1s inhibitors. By replacing isoquinoline with 1-aminophthalazine, we enhanced the C1s inhibitory activity while maintaining good selectivity against other serine proteases. Through structure-based optimization around the S2 and S3 sites and improving membrane permeability, we identified (R)-8 as a potent, selective, orally available, and brain-penetrable C1s inhibitor, which effectively blocked the classical complement pathway.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Medicine, General & Internal
Huange Zhu
Summary: The squamous cell carcinoma antigen (SCCA) has potential clinical value as a tumor marker, but its diagnostic and prognostic accuracy is still controversial. Standardized detection methods and scoring systems need to be established, and dynamic observation is necessary.
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
Immunology
Felix I. L. Clanchy, Yi-Shu Huang, Joy Ogbechi, L. Gail Darlington, Richard O. Williams, Trevor W. Stone
Summary: This study reports that several proteases associated with tumorigenesis can induce the expression of IDO1 and generate immunosuppressive kynurenine. These proteases also induce the production of inflammatory cytokines. The findings reveal a novel mechanism for activating IDO1 and provide a new target for tumor treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Tim Van Kersavond, Raphael Konopatzki, Merel A. T. van der Plassche, Jian Yang, Steven H. L. Verhelst
Summary: Rhomboid proteases are important enzymes involved in various biological processes and human diseases. Recent research has shown that solid-phase synthesis of peptidyl alpha-ketoamides allows rapid synthesis and optimization of rhomboid protease inhibitors, with the primed site binding part being crucial for potency.
Article
Plant Sciences
Juan Vorster, Willem van der Westhuizen, Gedion du Plessis, Diana Marais, Francesca Sparvoli, Eleonora Cominelli, Emanuela Camilli, Marika Ferrari, Cinzia Le Donne, Stefania Marconi, Silvia Lisciani, Alessia Losa, Tea Sala, Karl Kunert
Summary: Proteases and protease inhibitors play important roles throughout the life cycle of plants, but their functions in seed development are not fully understood. Specific serine protease inhibitors may affect seed development and require further investigation.
FRONTIERS IN PLANT SCIENCE
(2023)
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
Oncology
Danielle S. Bitterman, Ming-Hui Chen, Jing Wu, Andrew A. Renshaw, Marian Loffredo, Philip W. Kantoff, Eric J. Small, Anthony V. D'Amico
Summary: This study found that low testosterone level at PSA failure in high-risk patients with PC treated with RT is associated with increased PCSM and ACM risk, and that higher PSAn is also associated with worse PCSM and ACM risk, especially in men with normal testosterone levels at PSA failure.
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)
Article
Chemistry, Multidisciplinary
Scott Lovell, Leran Zhang, Thomas Kryza, Anna Neodo, Nathalie Bock, Elena De Vita, Elizabeth D. Williams, Elisabeth Engelsberger, Congyi Xu, Alexander T. Bakker, Maria Maneiro, Reiko J. Tanaka, Charlotte L. Bevan, Judith A. Clements, Edward W. Tate
Summary: Kallikrein-related peptidases (KLKs) play important roles in prostate cancer, with significant decoupling between KLK activity and abundance. The proteolysis of KLK should be considered as an additional parameter for accurate diagnosis and monitoring of PCa, presenting a promising therapeutic target.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Yuto Kondo, Hiroyuki Kimura, Ichiro Sasaki, Shigeki Watanabe, Yasuhiro Ohshima, Yusuke Yagi, Yasunao Hattori, Manami Koda, Hidekazu Kawashima, Hiroyuki Yasui, Noriko S. Ishioka
Summary: Copper-mediated nucleophilic radiochemistry using a boronic precursor is a promising method for the synthesis of PSMA imaging probes, improving the radiochemical yields.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)