Article
Chemistry, Medicinal
Shuvechha Chakraborty, Kshitija Rahate, Chandan Kumar, Susan Idicula-Thomas
Summary: This study systematically investigated the druggability of Candida proteome and discovered two SAP inhibitors that can significantly reduce the dosage of fluconazole required for Candida inhibition. Wet-lab validation confirmed their inhibitory activity on par with pepstatin A, a known inhibitor of aspartyl proteases.
DRUG DEVELOPMENT RESEARCH
(2023)
Article
Microbiology
Pavla Snebergerova, Pavla Bartosova-Sojkova, Marie Jalovecka, Daniel Sojka
Summary: Apicomplexan genomes encode multiple pepsin-family aspartyl proteases that have diversified to adapt to different strategies of host infection and transmission. Expressional profiling of Babesia microti APs and phylogenetic analysis of APs from selected Babesia and Theileria species indicate their potential roles and druggable enzymatic targets for specific therapy for babesiosis.
Article
Chemistry, Medicinal
Henry R. O'Donnell, Tia A. Tummino, Conner Bardine, Charles S. Craik, Brian K. Shoichet
Summary: This study reveals that many drugs repurposed for combating COVID-19 in biochemical assays are actually artifacts, and suggests that even drugs can act artifactually via colloidal aggregation at screening-relevant concentrations.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Lachlan W. Richardson, Trent D. Ashton, Madeline G. Dans, Nghi Nguyen, Paola Favuzza, Tony Triglia, Anthony N. Hodder, Anna Ngo, Kate E. Jarman, Alan F. Cowman, Brad E. Sleebs
Summary: Plasmepsin X is an important aspartyl protease in the invasion and egression of Plasmodium parasites. In this study, peptidomimetics were designed to inhibit Plasmepsin X and effectively arrested the development of asexual Plasmodium falciparum parasites. These findings are significant for understanding the substrate specificity of Plasmepsin X and designing future antimalarial drugs.
Article
Chemistry, Medicinal
Masahiko Taguchi, Ryo Oyama, Masahiro Kaneso, Shigehiko Hayashi
Summary: This study investigates the effects of drug-resistant mutants of HIV-1 protease on inhibitor binding through molecular simulation, and successfully elucidates the molecular mechanism of drug resistance.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Gordon J. Lockbaum, Linah N. Rusere, Mina Henes, Klajdi Kosovrasti, Desaboini Nageswara Rao, Ean Spielvogel, Sook-Kyung Lee, Ellen A. Nalivaika, Ronald Swanstrom, Nese Kurt Yilmaz, Celia A. Schiffer, Akbar Ali
Summary: Protease inhibitors are powerful antivirals against HIV-1, but their effectiveness is reduced against resistant variants. Enhancing resistance profiles is crucial for developing more robust inhibitors, which could be promising for simplified next-generation antiretroviral therapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Allergy
Ahmed O. Shalash, Luke Becker, Jieru Yang, Paul Giacomin, Mark Pearson, Waleed M. Hussein, Alex Loukas, Istvan Toth, Mariusz Skwarczynski
Summary: This study compared the protective efficacy of peptide vaccines and a clinical vaccine, and found that peptide vaccines based on p3 provided safer and higher protection against hookworm infection compared with the clinical vaccine Na-APR-1.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Linda Cerofolini, Kristian Vasa, Elisa Bianconi, Maria Salobehaj, Giulia Cappelli, Alice Bonciani, Giulia Licciardi, Anna Perez-Rafols, Luis Padilla-Cortes, Sabrina Antonacci, Domenico Rizzo, Enrico Ravera, Caterina Viglianisi, Vito Calderone, Giacomo Parigi, Claudio Luchinat, Antonio Macchiarulo, Stefano Menichetti, Marco Fragai
Summary: Several protein-drug conjugates are currently used in cancer therapy, relying on covalently attached cytotoxic organic compounds or non-covalent interactions. Human transthyretin (TTR) has been identified as a potential carrier protein for cytotoxic drug delivery. This study demonstrates the importance of integrating multiple biophysical and structural techniques, such as microscale thermophoresis, X-ray crystallography, and NMR. Solid-state NMR is particularly valuable in revealing ligand binding effects and their impact on macromolecular complex stability.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Pharmacology & Pharmacy
Dejuan Sun, Yuanyuan Guo, Piyu Tang, Hua Li, Lixia Chen
Summary: ADP-ribosylation factor 6 (Arf6), a small G-protein, plays important roles in cellular events and cancer progression. Understanding its function and mechanism is essential for future cancer therapy. This review summarizes the structure and roles of Arf6 in cancer, and discusses its potential as a target for protein-protein interaction inhibitors.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biotechnology & Applied Microbiology
Hyun Oh Yang, Yong-Joon Cho, Jae Min Lee, Kyoung-Dong Kim
Summary: Malassezia and Staphylococcus are the dominant genera in human skin microbiome. The study investigated the transcriptional changes in these two genera when co-cultured. It was found that co-culturing led to upregulation of ribosomal protein encoding genes and downregulation of aspartyl protease encoding genes in M. restricta. Moreover, it was observed that M. restricta secreted biomolecules, such as aspartyl proteases, that degraded the biofilm structure of S. aureus.
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Leandro Rocha Silva, Ari Souza Guimaraes, Jadiely do Nascimento, Igor Jose do Santos Nascimento, Elany Barbosa da Silva, James H. McKerrow, Silvia Helena Cardoso, Edeildo Ferreira da Silva-Junior
Summary: This study evaluated the structures of CRZ and RhD, identifying a potent inhibitory molecule. Through virtual screening and dynamic simulations, several promising inhibitors were found, with JN-11 showing time-dependent and reversible inhibition.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Yang Chen, Guibin Wang, Wen Zhang, Ying Han, Libo Zhang, Hubo Xu, Shiqiu Meng, Lin Lu, Yanxue Xue, Jie Shi
Summary: This study found that rats with compulsive cocaine use showed increased neural activity in the anterior insular cortex and enhanced orbitofrontal cortex-anterior insular cortex circuit. Manipulating the activity of anterior insular cortex glutamatergic neurons and the orbitofrontal cortex-anterior insular cortex circuit bidirectionally regulated compulsive cocaine intake.
Article
Multidisciplinary Sciences
Marzieh Sohrabi, Mohammad Nazari Montazer, Sara Moghadam Farid, Nader Tanideh, Mehdi Dianatpour, Ali Moazzam, Kamiar Zomorodian, Somayeh Yazdanpanah, Mehdi Asadi, Samanesadat Hosseini, Mahmood Biglar, Bagher Larijani, Massoud Amanlou, Maliheh Barazandeh Tehrani, Aida Iraji, Mohammad Mahdavi
Summary: The present study synthesized a series of thioquinazolinone derivatives conjugated with nitrothiazolacetamide and investigated their inhibitory activity against urease. Compound 8h exhibited the strongest inhibitory activity and showed high anti-ureolytic activity against two urease-positive microorganisms. Molecular docking study revealed that 8h interacted with multiple residues and demonstrated good hydrophobicity against urease.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Guolyu Xu, Huizhao Su, Lining Lu, Xiaomeng Liu, Liang Zhao, Bo Tang, Zhenhua Ming
Summary: This study reports the structural characteristics of ubiquitin-specific protease 34 (USP34) and the mechanism of ubiquitin recognition. The results show that upon binding with ubiquitin, the conformation of USP34 changes, and the catalytic triad is rearranged. This structural transition is closely related to the gripping of ubiquitin by the fingertips of USP34.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Organic
Tyson F. Belz, Mingliang Lin, Lisa M. Eubanks, Beverly Ellis, Kim D. Janda
Summary: The H-2P vaccine generated a catalytic antibody response in rodents, leading to high levels of morphine due to antibody catalysis and showing significance in behavioral assays. This provides a starting point for developing monoclonal catalytic antibodies against heroin.
TETRAHEDRON LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Rafael G. Silva, D. Randal Kipp, Vern L. Schramm
Article
Biochemistry & Molecular Biology
D. Randal Kipp, Christopher M. Quinn, Pascal D. Fortin
Article
Chemistry, Multidisciplinary
D. Randal Kipp, Rafael G. Silva, Vern L. Schramm
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2011)
Article
Biochemistry & Molecular Biology
Virginia Fonte, D. Randal Kipp, John Yerg, David Merin, Margaret Forrestal, Eileen Wagner, Christine M. Roberts, Christopher D. Link
JOURNAL OF BIOLOGICAL CHEMISTRY
(2008)