Article
Cell Biology
Sujata B. Walunj, Manisha M. Dias, Chhaminder Kaur, Kylie M. Wagstaff, Vishakha Dey, Caroline Hick, Swati Patankar, David A. Jans
Summary: This study reveals the potential of IMP alpha proteins from Plasmodium falciparum and Toxoplasma gondii as targets for small molecule inhibitors. Through high-throughput screening, compounds that inhibit the binding of P. falciparum IMP alpha to a P. falciparum NLS were identified and shown to limit the growth of both P. falciparum and T. gondii. These findings suggest that apicomplexan IMP alpha proteins could be therapeutic targets for the development of novel agents against these neglected parasitic diseases.
Article
Engineering, Environmental
L. Szydlowski, J. Ehlich, I. Goryanin, G. Pasternak
Summary: The study compared the electroactive capabilities of microbial communities from four mine drainages using a newly designed 96-well-plate array of microbial fuel cells. It demonstrated that the 96-well MFC array is a suitable platform for high-throughput screening, selection, and enrichment of electroactive consortia. Environmental conditions and physical and chemical parameters were found to be crucial for developing an efficient electroactive community.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Arun Bahadur Gurung, Jigmi Tshering Bhutia, Atanu Bhattacharjee
Summary: This study used a structure-based virtual screening approach to identify potential inhibitors of Vanin-1. Three lead molecules were found to form hydrogen bonds with catalytic residues and cause alterations in the enzyme's geometric properties. Molecular dynamics simulation showed that the lead molecules reduced the fluctuations in Vanin-1 and remained stable throughout the simulation period. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) studies indicated that van der Waals interaction energy significantly contributed to the binding free energy. These findings suggest that the lead molecules could serve as potential inhibitors of Vanin-1 for further investigation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Medicinal
Lydia Mata-Cantero, Stanley C. Xie, Mercedes Garcia, Joanne Coyle, Raquel Fernandez, Alvaro Cortes Cabrera, David L. Gillett, Benigno Crespo, Francisco-Javier Gamo, Esther Fernandez, Leann Tilley, Maria G. Gomez-Lorenzo
Summary: Through screening compounds, this study identified four chemical families with selectivity for the P. falciparum proteasome, providing a good starting point for the development of new antimalarial drugs.
ACS INFECTIOUS DISEASES
(2021)
Article
Chemistry, Medicinal
Medve Laura, Gealageas Ronan, Lam Bao Vy, Guillaume Valentin, Castillo-Aguilera Omar, Camberlein Virgyl, Catherine Piveteau, Rosell Melissa, Fleau Charlotte, Warenghem Sandrine, Charton Julie, Dumont-Ryckembusch Julie, Bosc Damien, Leroux Florence, van Endert Peter, Deprez Benoit, Deprez-Poulain Rebecca
Summary: ERAP2 is an emerging pharmacological target in cancer immunotherapy and autoinflammatory disease control, and selective inhibitors and activators have been identified in this study, which could serve as useful starting points for further optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biology
Giacomo Paonessa, Giulia Siciliano, Rita Graziani, Cristiana Lalli, Ottavia Cecchetti, Cristina Alli, Roberto La Valle, Alessia Petrocchi, Alessio Sferrazza, Monica Bisbocci, Mario Falchi, Carlo Toniatti, Alberto Bresciani, Pietro Alano
Summary: High-throughput screening and validation assays have identified potential antimalarial drugs that can kill both sexual and asexual blood stages of Plasmodium falciparum, thus blocking parasite transmission through mosquitoes.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Medicinal
Shagun Krishna, Brian Berridge, Nicole Kleinstreuer
Summary: This study investigated the relationship between environmental chemicals and cardiovascular diseases using Tox21/ToxCast HTS data, identifying specific chemicals with bioactivity against cardiovascular targets. Through ranking and clustering, chemicals affecting cardiovascular biology were prioritized for further testing and potential implications in adverse cardiovascular outcomes.
CHEMICAL RESEARCH IN TOXICOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Zhidong Zhang, Qi Guo, Yuetong Wang, He Huang
Summary: Microfluidics plays a crucial role in green biomanufacturing by genetically modifying microbial chassis to synthesize desired products. Droplet-based microfluidics has been successfully applied to various microbes, enabling the detection of massive metabolites. In summary, droplet microfluidics has evolved into a powerful technology for high-throughput screening in the green biomanufacturing industry.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biology
Hani Choudhry
Summary: This study aimed to identify potential inhibitors for the ADAR1 protein that bind to the Za domain using molecular docking and simulation tools. Three compounds-alendronate, etidronate, and zoledronate-were identified as top potential inhibitors and characterized for their interactions with the Z-RNA domain through simulations, providing novel insights for repurposing drugs to inhibit ADAR1 function.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Scott Legare, Fabian Heide, Ben A. Bailey-Elkin, Jorg Stetefeld
Summary: This study reports the biophysical and enzymatic characterization of the coronavirus main protease (M-pro) and evaluates its suitability for high-throughput screening. The researchers developed an improved substrate for screening and discovered a framework for designing M-pro enzyme assays to facilitate the discovery and development of therapies targeting M-pro.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yiwei Zhang, Jiabei Guo, Jiongjia Cheng, Zhenghua Zhang, Fenghua Kang, Xiaoxing Wu, Qian Chu
Summary: Therapeutic peptides have revolutionized treatment for many human diseases. In recent decades, stapled helical peptides have made rapid progress in drug discovery. Compared to unstabilized linear peptides, stapled helical peptides have shown superior binding affinity, selectivity, membrane permeability, and metabolic stability, offering exciting potential for targeting challenging protein-protein interfaces. This Perspective summarizes the recent use of high-throughput screening technologies for identifying potent stapled helical peptides with optimized binding properties, aiming to accelerate the development of stapled helical peptides as the next generation of therapeutic peptides for various human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Yi Lu, Kai-Wolfgang Hintzen, Tetiana Kurkina, Yu Ji, Ulrich Schwaneberg
Summary: Polylactic acid (PLA) is considered as a promising biopolymer to replace petrochemical-based polymers and is often blended with other polymers like polypropylene (PP) for improved properties. A technical challenge in recycling PLA/PP blends is the separation of PLA from PP. This study reports the development of a protein engineering approach to improve the material-specific binding of PLA by designing material binding peptides (MBPs) and successfully obtaining a variant with 2.3-fold improved PLA binding specificity compared to PP. The established screening platform provides a general methodology for designing material-specific MBPs for applications in PLA detection, sorting, and degradation in mixed plastics.
Article
Virology
Anushka Ramjag, Sergej Cutrone, Kai Lu, Christine Crasto, Jing Jin, Sonia Bakkour, Christine V. F. Carrington, Graham Simmons
Summary: This study describes a high-throughput method for screening inhibitors of alphavirus budding and identifies several antibodies with potent anti-budding activity. The findings provide important candidates for the development of therapeutics and prophylaxis against CHIKV and MAYV.
Article
Multidisciplinary Sciences
Anuradha Kumar, Somsundaram Chettiar, Brian S. Brown, Julie Early, Juliane Ollinger, Megan Files, Mai A. Bailey, Aaron Korkegian, Devon Dennison, Matthew McNeil, James Metz, Augustine Osuma, Michael Curtin, Aaron Kunzer, Gail Freiberg, Milan Bruncko, Dale Kempf, Tanya Parish
Summary: A high-throughput phenotypic screening of a diverse chemical library identified 24 chemotypes with anti-tubercular activity. Further exploration revealed that MmpL3 may serve as the target or mechanism of resistance for these compounds.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Jie Li, Yan Zhou, Guy Eelen, Qing-tong Zhou, Wen-bo Feng, Viktorija Labroska, Fen-fen Ma, Hui-ping Lu, Mieke Dewerchin, Peter Carmeliet, Ming-wei Wang, De-hua Yang
Summary: The growth of solid tumors relies on tumor vascularization and endothelial cells. Targeting the glycolytic activity of endothelial cells can normalize tumor vessels, reduce metastasis, and improve chemotherapy outcomes.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Pharmacology & Pharmacy
Vincent Blay, Bhairavi Tolani, Sunita P. Ho, Michelle R. Arkin
DRUG DISCOVERY TODAY
(2020)
Article
Chemistry, Medicinal
Xavier Guillory, Madita Wolter, Seppe Leysen, Joao Filipe Neves, Ave Kuusk, Sylvia Genet, Bente Somsen, John Kenneth Morrow, Emma Rivers, Lotte van Beek, Joe Patel, Robert Goodnow, Heike Schoenherr, Nathan Fuller, Qing Cao, Richard G. Doveston, Luc Brunsveld, Michelle R. Arkin, Paola Castaldi, Helen Boyd, Isabelle Landrieu, Hongming Chen, Christian Ottmann
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Correction
Immunology
Andrew S. Mendiola, Jae Kyu Ryu, Sophia Bardehle, Anke Meyer-Franke, Kenny Kean-Hooi Ang, Chris Wilson, Kim M. Baeten, Kristina Hanspers, Mario Merlini, Sean Thomas, Mark A. Petersen, Alexander Williams, Reuben Thomas, Victoria A. Rafalski, Rosa Meza-Acevedo, Reshmi Tognatta, Zhaoqi Yan, Samuel J. Pfaff, Michael R. Machado, Catherine Bedard, Pamela E. Rios Coronado, Xiqian Jiang, Jin Wang, Michael A. Pleiss, Ari J. Green, Scott S. Zamvil, Alexander R. Pico, Benoit G. Bruneau, Michelle R. Arkin, Katerina Akassoglou
Article
Biochemical Research Methods
May H. Abdel Aziz, Yao Fan, Lijun Liu, Mark M. Moasser, Haian Fu, Natalia Jura, Michelle R. Arkin
Summary: This study evaluated the use of Pichia pastoris as a host for expression of human kinases and showed that addition of the VLK domain improved expression and decreased aggregation of certain kinases. Some kinases were purified with good yield, purity, and comparable activity to commercially available versions.
PROTEIN EXPRESSION AND PURIFICATION
(2021)
Article
Biochemistry & Molecular Biology
Eline Sijbesma, Bente A. Somsen, Galen P. Miley, Iris A. Leijten-van de Gevel, Luc Brunsveld, Michelle R. Arkin, Christian Ottmann
ACS CHEMICAL BIOLOGY
(2020)
Article
Microbiology
Rahul Tyagi, Christina A. Bulman, Fidelis Cho-Ngwa, Chelsea Fischer, Chris Marcellino, Michelle R. Arkin, James H. McKerrow, Case W. McNamara, Matthew Mahoney, Nancy Tricoche, Shabnam Jawahar, James W. Janetka, Sara Lustigman, Judy Sakanari, Makedonka Mitreva
Summary: 18 hits with anti-macrofilaricidal activity were identified, with azoles and aspartic protease inhibitors being prioritized for further study. These drugs showed activity against Onchocerca spp. as well, with the potential to identify selective drugs that prevent adverse events in co-infected individuals.
Article
Chemistry, Medicinal
Eline Sijbesma, Kenneth K. Hallenbeck, Sebastian A. Andrei, Reanne R. Rust, Joris M. C. Adriaans, Luc Brunsveld, Michelle R. Arkin, Christian Ottmann
Summary: The systematic discovery of functional fragments that bind to the composite interface of protein complexes is a critical step towards developing orthosteric stabilizers for protein-protein interactions (PPIs). By evaluating structure-activity relationships, it was found that covalent fragments engaging a relatively large and exposed binding pocket at the protein/peptide interface with a molecular glue mode of action can stabilize PPIs.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Marcus Y. Chin, Anand R. Patwardhan, Kean-Hooi Ang, Austin L. Wang, Carolina Alquezar, Mackenzie Welch, Phi T Nguyen, Michael Grabe, Anna Molofsky, Michelle R. Arkin, Aimee W. Kao
Summary: A novel genetically encoded fluorescent protein-based pH biosensor called FIRE-pHLy was designed to better understand lysosomal pH, enabling ratiometric quantification and targeting lysosomes with LAMP1. The biosensor reported lumenal pH between 3.5 and 6.0 with mTFP1 and enabled quantification of the alkalinizing response to bafilomycin Al in various cellular models. FIRE-pHLy is a specific, robust, and versatile lysosomal pH biosensor with broad applications in investigating pH dynamics in aging- and lysosome-related diseases and lysosome-based drug discovery.
Article
Biochemistry & Molecular Biology
Marcus Y. Chin, Kean-Hooi Ang, Julia Davies, Carolina Alquezar, Virginia G. Garda, Brendan Rooney, Kun Leng, Martin Kampmann, Michelle R. Arkin, Aimee W. Kao
Summary: The study aimed to identify small molecules that acidify lysosomal pH and molecular targets/pathways that regulate lysosomal pH. Using a new lysosomal pH biosensor, a high-throughput screening assay identified two compounds, OSI-027 and PP242, as top acidifying hits, which may be used to investigate potential therapeutic pathways for neurodegenerative diseases such as autophagy activation and lysosomal acidification.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Ziwen Jiang, Yu-Hsuan Kuo, Mengqi Zhong, Jianchao Zhang, Xin X. Zhou, Lijuan Xing, James A. Wells, Yanzhuang Wang, Michelle R. Arkin
Summary: Protein-protein interactions (PPIs) play crucial roles in cellular signaling and functions. Precise modulation of PPIs can help understand their roles in cellular events and be therapeutically valuable. In this study, an antibody fragment-based modulator for the PPI between p97 and its adaptor protein NSFL1C was developed, demonstrating its potential application in therapeutic interventions by disrupting specific intracellular PPIs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Yinyan Tang, Amber Kay, Ziwen Jiang, Michelle R. Arkin
Summary: Autophagy is a cellular process that degrades unwanted proteins and organdies by lysosomes. The interaction between LC3B and ATG4b is studied in this research, and it is found that LC3B-115, the core of LC3B, binds tightly to full-length ATG4b and inhibits its cleavage of pro-LC3B. The C-terminal tail of ATG4b contributes significantly to the binding affinity of LC3B-ATG4b interaction and wraps around the LC3B-ubiquitin core. These findings support a bipartite model for LC3B-ATG4b binding.
Article
Multidisciplinary Sciences
Megan L. Koleske, Gregory McInnes, Julia E. H. Brown, Neil Thomas, Keino Hutchinson, Marcus Y. Chin, Antoine Koehl, Michelle R. Arkin, Avner Schlessinger, Renata C. Gallagher, Yun S. Song, Russ B. Altman, Kathleen M. Giacomini
Summary: This study investigated the impact of variants in the SLC22A5 gene on the function of the carnitine transporter protein OCTN2 and created a predictive model. The results showed that most variants reduced carnitine transport, with some severely impairing function by at least 80%. Additionally, the study identified a major mechanism causing the loss of OCTN2 function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Ziwen Jiang, Yu-Hsuan Kuo, Michelle R. Arkin
Summary: Autophagy is a crucial process for the degradation of large cellular contents, and impaired autophagy can lead to pathological aggregation. This study developed a novel method for targeted degradation of protein aggregates and organelles in mammalian cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Julian R. Braxton, Chad R. Altobelli, Maxwell R. Tucker, Eric Tse, Aye C. Thwin, Michelle R. Arkin, Daniel R. Southworth
Summary: This study reports the structures of p97 protein bound to the UBXD1 adaptor and identifies UBXD1 as a potent ATPase inhibitor of p97. The structures, mutagenesis, and comparisons with other adaptors reveal how UBXD1 regulates the ATPase activity and structure of p97.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Marcus Y. Chin, Jether Amos Espinosa, Grace Pohan, Sarine Markossian, Michelle R. Arkin
Summary: Organelles play crucial roles in sustaining life and their dysfunction can lead to various diseases. The development of specifically targeted fluorescent probes is essential for accelerating drug discovery. Exploring organelle-specific morphology and dynamics, along with high-content analysis, can stimulate further development of probes and approaches for high-throughput screening of organelles.
CELL CHEMICAL BIOLOGY
(2021)