Article
Chemistry, Medicinal
Hengzhi Sun, Jinzheng Wang, Shengjie Liu, Xinyu Zhou, Liang Dai, Caiping Chen, Qinglong Xu, Xiaoan Wen, Keguang Cheng, Hongbin Sun, Haoliang Yuan
Summary: A potential binding pocket was identified on the PCSK9-LDLR PPI surface by induced-fit docking, leading to the discovery of novel small molecule inhibitors through virtual screening and biological evaluations. Compound 13 showed inhibitory activity against PCSK9-LDLR PPI and restored LDLR uptake function in HepG2 cells, indicating its potential as a lead compound for further development of small molecule inhibitors targeting PCSK9-LDLR PPI.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Multidisciplinary
Takumi Yokoyama, Takehiro Ando, Yukio Takamori, Daisuke Fuji, Masashi Sato, Santhana Vedi, Mizuki Yamamoto, Takashi Kawakami
Summary: This study reports a novel linker for SELEX of mRNA-displayed unnatural peptides, forming thioethers through intramolecular reactions.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Mirei Date, Ai Miyamoto, Tomoko Honjo, Tsugumi Shiokawa, Hiroko Tada, Nobuhiro Okada, Junichiro Futami
Summary: This study presents a practical method for large-scale autoantibody discovery using total cellular proteins from cultured mammalian cells. The researchers found that nucleic acid-free and fully denatured water-soluble total cellular proteins from mammalian cells were ideal for precise separation and analysis. They propose a novel two-dimensional gel electrophoresis system as an alternative method for large-scale autoantibody discovery.
Review
Pharmacology & Pharmacy
Johanna Giovannini, Willy Smeralda, Marie Jouanne, Jana Sopkova-de Oliveira Santos, Marco Catto, Anne Sophie Voisin-Chiret
Summary: Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein in the brain, with Alzheimer's disease being the most common form. The pathophysiological mechanisms of AD are still not fully understood, and there is currently no curative treatment available. Therefore, targeting tau protein aggregation has become an important focus for therapeutic approaches.
DRUG DISCOVERY TODAY
(2022)
Review
Pharmacology & Pharmacy
Honggang Xiang, Mi Zhou, Yan Li, Lu Zhou, Renxiao Wang
Summary: Autophagy is a cellular process that involves the engulfment and degradation of proteins and organelles through protein-protein interactions. Targeting selective regulation of these interactions provides a new opportunity for autophagy regulation with lower risk of off-target effects. This article provides background knowledge on critical protein-protein interactions in autophagy and reviews successful attempts in discovering regulators targeting these interactions. It also discusses successful strategies and existing limitations in this field.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Multidisciplinary Sciences
Philipp Koch, Steven Schmitt, Mathias Cardner, Niko Beerenwinkel, Sven Panke, Martin Held
Summary: The number of newly approved antimicrobial compounds has been decreasing, highlighting the need for novel antimicrobial substances. This study presents a high-throughput method called Me-x, which uses E. coli self-screening to identify the bioactivity of over ten thousand naturally occurring peptides. By analyzing E. coli growth curves using next-generation sequencing, more than 1000 previously unknown antimicrobial peptides are discovered. Additionally, the mode of action of these peptides is determined based on growth inhibition kinetics. The most promising peptides are synthesized and their activity is tested in standardized susceptibility assays, resulting in the discovery of ten peptides that efficiently eradicate bacteria. This work represents a significant advancement in the high-throughput discovery of diverse antimicrobials.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Yan Wang, Xuping Xie, Pei-Yong Shi
Summary: Infections with mosquito-borne flaviviruses are a significant threat to public health, but there are currently no approved antiviral drugs for their treatment. The non-structural protein NS4B has emerged as a target for drug discovery due to its multiple roles in the virus life cycle. This review summarizes the latest knowledge on the structure and function of flavivirus NS4B, as well as the progress on antiviral compounds that target NS4B.
ANTIVIRAL RESEARCH
(2022)
Review
Chemistry, Medicinal
Dinesh S. Reddy, Anamika Sinha, Amit Kumar, Vipin K. Saini
Summary: Tuberculosis (TB) remains the leading cause of death from a single infectious agent, but the outbreak of SARS-CoV-2 has made tackling this disease even more challenging. Drug-resistant TB, long treatment regimens, and the synergistic effect with HIV are significant drawbacks. While there are several drugs available to treat TB, there is still a lack of rapid and accurate treatment options. Intensive research is necessary to discover newer molecular analogs to eliminate this disease. Repurposing known drugs and re-engineering old TB-drug families have led to the development of newer compounds with novel mechanisms to treat drug-resistant strains.
ARCHIV DER PHARMAZIE
(2022)
Review
Biology
Sung-Min Kang, Do-Hee Kim
Summary: Autophagy, a lysosome-dependent intracellular degradation machinery, is crucial in regulating cellular homeostasis and is associated with various diseases. Recent structural studies and discovery of modulators have identified targeting autophagy as a promising strategy for novel drug development.
Article
Chemistry, Multidisciplinary
Christian E. Stieger, Yerin Park, Mark A. R. de Geus, Dongju Kim, Christiane Huhn, J. Sophia Slenczka, Philipp Ochtrop, Judith M. Muechler, Roderich D. Suessmuth, Johannes Broichhagen, Mu-Hyun Baik, Christian P. R. Hackenberger
Summary: We have discovered ethynyl-triazolyl-phosphinates (ETPs) as a new class of electrophilic warheads with cysteine selectivity for bioconjugation. Through Cu-I-catalyzed azide alkyne cycloaddition (CuAAC), various functional electrophilic building blocks, including proteins, were obtained from diethynyl-phosphinate. ETP-reagents were used to create fluorescent peptide-conjugates for receptor labeling on live cells and stable and biologically active antibody-drug conjugates. The excellent cysteine selectivity of ETP-electrophiles was demonstrated in mass spectrometry-based, proteome-wide cysteine profiling, highlighting their potential for homogeneous bioconjugation strategies to connect complex biomolecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Crhisllane Rafaele dos Santos Vasconcelos, Antonio Mauro Rezende
Summary: Leishmaniasis, a neglected infectious disease, was studied using computational methods to evaluate potential drug targets in the predicted proteomes of Leishmania braziliensis and Leishmania infantum, revealing several untested proteins with potential therapeutic value.
FRONTIERS IN CHEMISTRY
(2021)
Article
Nanoscience & Nanotechnology
Patricia Alamo, Eloi Parlade, Marianna T. P. Favaro, Alberto Gallardo, Rosa Mendoza, Luis C. S. Ferreira, Nerea Roher, Ramon Mangues, Antonio Villaverde, Esther Vazquez
Summary: Secretory protein microparticles are bio-inspired materials that mimic secretory granules in the human endocrine system. They are self-contained protein delivery platforms that slowly release proteins. By using cationic Zn for assembly, these granules are expected to be nontoxic and suitable for clinical use. However, their biosafety and protein dosage threshold have not been confirmed.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Biochemical Research Methods
Yuwei Zhou, Ziru Huang, Wenzhen Li, Jinyi Wei, Qianhu Jiang, Wei Yang, Jian Huang
Summary: Antibody drugs have become essential in biotherapeutics and have benefited patients with various diseases. However, their development process is time-consuming, costly, and risky. To accelerate development, reduce costs, and increase success rates, artificial intelligence, particularly deep learning methods, are extensively used in all stages of preclinical antibody drug development. This review systematically summarizes the use of deep learning in antibody drug discovery and development, including antibody encodings, deep learning architectures, and models. We also critically discuss the challenges, opportunities, current applications, and future directions of deep learning in antibody drug development.
Review
Chemistry, Multidisciplinary
Lin-hui Zhai, Kai-feng Chen, Bing-bing Hao, Min-jia Tan
Summary: Protein post-translational modifications (PTMs) are crucial for protein activity regulation and are involved in diseases. PTM regulatory enzymes are important drug targets. Mass spectrometry-based proteomics enables systematic characterization of PTMs for drug target identification, mechanism elucidation and biomarker discovery in personalized therapy.
ACTA PHARMACOLOGICA SINICA
(2022)
Review
Pharmacology & Pharmacy
Jia Fu, Wei Qin, Lu-Qi Cao, Zhe-Sheng Chen, Hui-Ling Cao
Summary: This review summarizes the applications and immobilization methods of receptor chromatography, which is widely used for high-throughput separation and accurate drug screening. The review focuses on screening active compounds in natural products, as well as the design and application of receptor chromatography in drug-receptor interactions.
DRUG DISCOVERY TODAY
(2023)
Article
Biochemical Research Methods
Nina Prokoph, Mats Ormo, Gavin O'Mahony, Anders Hogner, Jane McPheat, Ulla Karlsson, Lovisa Holmberg Schiavone, Jianming Liu
ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
(2016)
Article
Chemistry, Medicinal
Anneli Nordqvist, Gavin O'Mahony, Maria Friden-Saxin, Marlene Fredenwall, Anders Hogner, Kenneth L. Granberg, Anna Aagaard, Stefan Backstrom, Anders Gunnarsson, Tim Kaminski, Yafeng Xue, Anita Dellsen, Eva Hansson, Pia Hansson, Ida Ivarsson, Ulla Karlsson, Krister Bamberg, Majlis Hermansson, Jennie Georgsson, Bo Lindmark, Karl Edman
Review
Pharmacology & Pharmacy
Sebastian A. Andrei, Eline Sijbesma, Michael Hann, Jeremy Davis, Gavin O'Mahony, Matthew W. D. Perry, Anna Karawajczyk, Jan Eickhoff, Luc Brunsveld, Richard G. Doveston, Lech-Gustav Milroy, Christian Ottmann
EXPERT OPINION ON DRUG DISCOVERY
(2017)
Article
Chemistry, Medicinal
Loes M. Stevers, Eline Sijbesma, Maurizio Botta, Carol MacKintosh, Tomas Obsil, Isabelle Landrieu, Ylenia Cau, Andrew J. Wilson, Anna Karawajczyk, Jan Eickhoff, Jeremy Davis, Michael Hann, Gavin O'Mahony, Richard G. Doveston, Luc Brunsveld, Christian Ottmann
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Kenneth L. Granberg, Zhong-Qing Yuan, Bo Lindmark, Karl Edman, Johan Kajanus, Anders Hogner, Marcus Malmgren, Gavin O'Mahony, Anneli Nordqvist, Jan Lindberg, Stefan Tangefjord, Michael Kossenjans, Christian Lofberg, Jonas Branalt, Dongmei Liu, Nidhal Selmi, Grigorios Nikitidis, Peter Nordberg, Ahlke Hayen, Anna Aagaard, Eva Hansson, Majlis Hermansson, Ida Ivarsson, Rasmus Jansson-Lofmark, Ulla Karlsson, Ulrika Johansson, Lena William-Olsson, Judith Hartleib-Geschwindner, Krister Bamberg
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Dustin K. Bauknight, Victoria Osinski, Siva Sai Krishna Dasa, Anh T. Nguyen, Melissa A. Marshall, Julia Hartman, Matthew Harms, Gavin O'Mahony, Jeremie Boucher, Alexander L. Klibanov, Coleen A. McNamara, Kimberly A. Kelly
Article
Endocrinology & Metabolism
Tobias Kroon, Matthew Harms, Stefanie Maurer, Laurianne Bonnet, Ida Alexandersson, Anna Lindblom, Andrea Ahnmark, Daniel Nilsson, Peter Gennemark, Gavin O'Mahony, Victoria Osinski, Coleen McNamara, Jeremie Boucher
MOLECULAR METABOLISM
(2020)
Article
Chemistry, Multidisciplinary
Francesco Bosica, Sebastian A. Andrei, Joao Filipe Neves, Peter Brandt, Anders Gunnarsson, Isabelle Landrieu, Christian Ottmann, Gavin O'Mahony
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Joao Filipe Neves, Olivia Petrvalska, Francesco Bosica, Francois-Xavier Cantrelle, Hamida Merzougui, Gavin O'Mahony, Xavier Hanoulle, Tomas Obsil, Isabelle Landrieu
Summary: Protein-protein interactions (PPIs) involving 14-3-3 proteins and Tau are potential targets for Alzheimer's disease treatment. Phosphorylation of Tau by PKA is crucial for the formation of a stable complex with 14-3-3 sigma, with an affinity in the 1-10 micromolar range. Each monomer of the 14-3-3 sigma dimer binds to two different phosphorylated peptides of Tau-PKA, suggesting a 2:1 stoichiometry for 14-3-3/Tau-PKA.
Article
Chemistry, Medicinal
Gavin O'Mahony, Jens Petersen, Margareta Ek, Rebecca Rae, Carina Johansson, Liu Jianming, Nina Prokoph, Fredrik Bergstrom, Krister Bamberg, Fabrizio Giordanetto, Bader Zarrouki, Daniel Karlsson, Anders Hogner
Summary: A new compound, 10, has been discovered to be a potent PPARγ binder and inhibitor of CDK-mediated phosphorylation of PPARγ Ser273, without classical PPARγ agonism. In animal models, compound 10 demonstrated an improvement in insulin sensitivity.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Jakob S. Pallesen, Claire C. Munier, Francesco Bosica, Sebastian A. Andrei, Karl Edman, Anders Gunnarsson, Giuseppina La Sala, Okky Dwichandra Putra, Sonja Srdanovic, Andrew J. Wilson, Lisa Wissler, Christian Ottmann, Matthew W. D. Perry, Gavin O'Mahony
Summary: The ubiquitously expressed glucocorticoid receptor (GR) is a nuclear receptor that controls a broad range of biological processes and is activated by steroidal glucocorticoids. GR is also regulated through protein-protein interactions (PPIs) with adapter proteins 14-3-3 outside the steroid-binding site, providing insights into noncanonical GR signaling and enabling the development of novel GR modulators.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Se-Hyung Park, Robert N. Helsley, Leila Noetzli, Ho-Chou Tu, Kristina Wallenius, Gavin O'Mahony, Jeremie Boucher, Jianming Liu, Samir Softic
Summary: This study presents a luminescence-based protocol to quantify KHK activity, which has been validated for accuracy and specificity through experiments involving knockdown and overexpression of KHK in vivo and in vitro.
Article
Medicine, Research & Experimental
Victoria Osinski, Dustin K. Bauknight, Siva Sai Krishna Dasa, Matthew J. Harms, Tobias Kroon, Melissa A. Marshall, James C. Garmey, Anh T. Nguyen, Julia Hartman, Aditi Upadhye, Prasad Srikakulapu, Andrea Zhou, Gavin O'Mahony, Alexander L. Klibanov, Kimberly A. Kelly, Jeremie Boucher, Coleen A. McNamara
Article
Endocrinology & Metabolism
Ewa Hellstrom-Lindahl, Ola Aberg, Cecilia Ericsson, Gavin O'Mahony, Peter Johnstrom, Stanko Skrtic, Olof Eriksson
ACTA DIABETOLOGICA
(2017)