Article
Pharmacology & Pharmacy
Shan Liu, Xiao-Bing Lan, Miao-Miao Tian, Chun-Hao Zhu, Lin Ma, Jia-Mei Yang, Juan Du, Ping Zheng, Jian-Qiang Yu, Ning Liu
Summary: Chronic pain poses a significant public health challenge, impacting patients' physical and psychological health as well as their quality of life. Current drug treatments for chronic pain often have limited efficacy and come with numerous side effects. The chemokine system, specifically the CCL2/CCR2 axis, plays a crucial role in the development and maintenance of chronic pain. Targeting this system through various approaches, such as siRNA, blocking antibodies, or small molecule antagonists, holds promise for managing chronic pain.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Naotaka Tsutsumi, Shoji Maeda, Qianhui Qu, Martin Vogele, Kevin M. Jude, Carl-Mikael Suomivuori, Ouliana Panova, Deepa Waghray, Hideaki E. Kato, Andrew Velasco, Ron O. Dror, Georgios Skiniotis, Brian K. Kobilka, K. Christopher Garcia
Summary: This study reports the cryo-electron microscopy structures of HCMV-encoded GPCRs US28 and US27 forming nonproductive and productive complexes with host G proteins, providing new insights into their functional mechanisms in viral pathogenesis.
Article
Biochemistry & Molecular Biology
Ya-Hsin Liu, Chia-Hsuan Chuang, Yi-Zong Lee, Eh-Tzen Lee, Chiao-Ling Lo, Chu-Ya Wu, Li-Kun Huang, Andreas Bikfalvi, Shih-Che Sue
Summary: Chemokine CXCL4L1, a more potent antiangiogenic ligand, exhibits binding specificity to CXCR3A and CXCR3B receptors. The molten globule property of CXCL4L1 causes its tetramer to dissociate into monomers, while native CXCL4 forms a stable tetramer structure. The binding affinity of CXCL4L1 is influenced by the combination of CXCR3A N-terminus and receptor extracellular loop 2, as well as sulfation on the tyrosine residues. In contrast, the CXCR3B N-terminal extension does not significantly enhance the binding of CXCL4 or CXCL4L1.
Article
Cell Biology
Stefanie Alexandra Eberle, Martin Gustavsson
Summary: Chemokine receptors play important roles in physiological and pathological processes, and have potential as drug targets. However, there are currently few approved drugs targeting these receptors. This study describes the application, optimization and validation of a homogenous Scintillation Proximity Assay (SPA) for real-time kinetic profiling of chemokine-chemokine receptor interactions, using ACKR3 and CXCL12 as examples.
Article
Biochemistry & Molecular Biology
Hiroyoshi Machida, Sumito Inoue, Akira Igarashi, Shinichi Saitoh, Keiko Yamauchi, Michiko Nishiwaki, Takako Nemoto, Yoichiro Otaki, Masamichi Sato, Kento Sato, Hiroshi Nakano, Sujeong Yang, Kodai Furuyama, Hiroaki Murano, Yu Ishibashi, Takahito Ota, Takashi Nakayama, Yoko Shibata, Masafumi Watanabe
Summary: The production of CCL17 by lung epithelial cells upon cigarette smoke exposure contributes to the accumulation of alveolar macrophages and the development of pulmonary emphysema. CCL17-induced production of CCL2 by macrophages plays a role in macrophage accumulation. These findings provide new insights into the pathogenesis of COPD.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Charles J. Buchanan, Ben Gaunt, Peter J. Harrison, Yun Yang, Jiwei Liu, Aziz Khan, Andrew M. Giltrap, Audrey Le Bas, Philip N. Ward, Kapil Gupta, Maud Dumoux, Tiong Kit Tan, Lisa Schimaski, Sergio Daga, Nicola Picchiotti, Margherita Baldassarri, Elisa Benetti, Chiara Fallerini, Francesca Fava, Annarita Giliberti, Panagiotis Koukos, Matthew J. Davy, Abirami Lakshminarayanan, Xiaochao Xue, Georgios Papadakis, Lachlan P. Deimel, Virginia Casablancas-Antras, Timothy D. W. Claridge, Alexandre M. J. J. Bonvin, Quentin J. Sattentau, Simone Furini, Marco Gori, Jiandong Huo, Raymond J. Owens, Christiane Schaffitzel, Imre Berger, Alessandra Renieri, James H. Naismith, Andrew J. Baldwin, Benjamin G. Davis
Summary: This study utilizes universal saturation transfer analysis to reveal the interaction between the novel coronavirus and glycan compounds, and identifies protein mutations related to pathogenicity and zoonosis.
Article
Biochemistry & Molecular Biology
Hongguang Ma, Mengchu Li, Piyusha P. Pagare, Huiqun Wang, Nima Nassehi, Edna J. Santos, S. Stevens Negus, Dana E. Selley, Yan Zhang
Summary: This study synthesized a series of bivalent ligands to investigate the functional interactions between opioid and chemokine receptors. Compound 1a showed promising antinociceptive effect and may serve as a novel chemical probe for developing more potent bivalent ligands for chronic pain management.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xinxin Huang, Juncheng Hao, Yan Qin Tan, Tao Zhu, Vijay Pandey, Peter E. Lobie
Summary: Patients with epithelial ovarian cancer are often diagnosed at an advanced stage, leading to poor overall prognosis. This review summarizes the functional significance of CXCL/CXCR chemokines in modulating EOC progression and discusses the current status and prospects of CXCR/CXCL-based theranostic strategies in EOC management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Yang Li, Shukun Han, Baokang Wu, Chongli Zhong, Yu Shi, Chao Lv, Lei Fu, Yizhou Zhang, Qi Lang, Zhiyun Liang, Yang Yu, Yu Tian
Summary: CXCL11 expression is higher in tumor tissue and has associations with prognosis, immune cell infiltration, tumor mutation burden, and microsatellite instability. Further investigation into CXCL11 may improve cancer therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Fisheries
Beibei Zhao, Jing Diao, Le Li, Hidehiro Kondo, Lei Li, Ikuo Hirono
Summary: This study identified and characterized the CXCR2 gene in Japanese flounder, showing that the expression levels of JfCXCR1 and JfCXCR2 increase significantly in response to bacterial infections, with JfCXCR1 potentially activated by bacterial infections and JfCXCR2 activated by both bacterial and viral infections to mediate the immune response. These findings contribute to understanding the functions of CXCR1 and CXCR2 in the fish immune system.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Zhaoqian Su, Kalyani Dhusia, Yinghao Wu
Summary: The binding of cell surface receptors with extracellular ligands triggers distinctive signaling pathways, leading to corresponding phenotypic variation of cells. These ligand-receptor complexes can further oligomerize into higher-order structures, playing an important role in regulating cell signaling functions. Structural differences between receptors contribute to varying dynamic properties and spatial patterns of the resulting oligomers.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Editorial Material
Biochemistry & Molecular Biology
Kaiwen Liu, Ling Shen, Meng Wu, Zhi-Jie Liu, Tian Hua
Summary: The study reveals the binding modes between CXCL8 and CXCR2, CXCR2 and G protein, as well as the detailed binding pattern of the allosteric antagonist 00767013. Further analysis also uncovers the unique shallow-pocket activation mechanism of CXCR2 and suggests a potential role of cholesterol in allosteric modulation in chemokine receptors.
Article
Chemistry, Multidisciplinary
Fei Kong, Huiyuan Bai, Ming Ma, Chen Wang, Haiyan Xu, Ning Gu, Yu Zhang
Summary: The utilization of a composite nanozyme to target and treat acute myeloid leukemia represents a potential therapeutic approach, alleviating the toxic side effects of chemotherapy and improving treatment efficacy.
Article
Chemistry, Multidisciplinary
Stefan Mordalski, Agnieszka Wojtuch, Igor Podolak, Rafal Kurczab, Andrzej J. Bojarski
Summary: Depicting a ligand-receptor complex via Interaction Fingerprints is a viable data visualization and analysis tool with a wide range of applications. The authors present a new tool derived from Structural Interaction Fingerprints to provide detailed insights into interactions between receptor and specific regions of the ligand. The tool is easy to use and extends the python library for generating interaction matrices.
JOURNAL OF CHEMINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Wei Gao, Yufen Wang, Jian Bi, Xiuli Chen, Na Li, Yingde Wang, Haiying Tang, Jingwei Mao
Summary: The abnormal crosstalk between gut immune system and liver in nonalcoholic steatohepatitis (NASH) may be related to the changes in the numbers and activity of CD4+ T cells and DC subsets. This imbalance in gut immunity in NASH could be due to impaired gut chemokine receptor 9 (CCR9)/chemokine ligand 25 (CCL25) signaling pathway.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Engineering, Industrial
Angelo K. S. Romasanta, Peter van der Sijde, Iwan J. P. de Esch
Summary: This study explores how researchers in big pharma firms engage with knowledge from an emerging field, and how they adapt their activities to overcome uncertainties. By focusing on internal and external activities, proponents of novel technologies bridge the developments in the field with the rest of the firm, leading to the adoption and development of the technology.
Article
Chemistry, Medicinal
Iwan J. P. de Esch, Daniel A. Erlanson, Wolfgang Jahnke, Christopher N. Johnson, Louise Walsh
Summary: The review summarizes successful fragment-to-lead studies published in 2020 and discusses trends and best practices in fragment libraries, target proteins, screening technologies, hit-optimization strategies, and properties of hit fragments and leads. Trends and innovations identified in the review promise to further increase the success of FBDD by developing novel screening fragments, improving screening technologies, using computer-aided design and virtual screening, and combining FBDD with other drug-discovery technologies.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
David J. Hamilton, Marieke Beemsterboer, Caroline M. Carter, Jasmina Elsayed, Rilana E. M. Huiberts, Hanna F. Klein, Peter O'Brien, Iwan J. P. de Esch, Maikel Wijtmans
Summary: Fragment-based drug discovery has a growing need for unique screening libraries. Cyclobutane moiety, identified as an attractive three-dimensional scaffold, was used to synthesize a library of novel 3D cyclobutane fragments. The library exhibited favorable shape and physicochemical properties compared to existing synthetic 3D fragment libraries.
Article
Chemistry, Medicinal
Gabor Wagner, Tamara A. M. Mocking, Xiaoyuan Ma, Inna Slynko, Daniel Da Costa Pereira, Robin Breeuwer, Niek J. N. Rood, Cas van der Horst, Henry F. Vischer, Chris de Graaf, Iwan J. P. de Esch, Maikel Wijtmans, Rob Leurs
Summary: In this study, the structure-activity relationship analysis of derivatives of ZEL-H16 revealed that both basic moieties and their distance from the central core are essential for H3R affinity. However, contrary to previous reports, ZEL-H16 and its derivatives were found to act as inverse agonists for G alpha(i) signaling in this study. Docking studies and molecular dynamics simulations identified ionic interactions/hydrogen bonds as crucial interaction points with H3R residues D114 and E206.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Yang Zheng, Susanne Schroeder, Georgi K. Kanev, Sanaa S. Botros, Samia William, Abdel-Nasser A. Sabra, Louis Maes, Guy Caljon, Carmen Gil, Ana Martinez, Irene G. Salado, Koen Augustyns, Ewald Edink, Maarten Sijm, Erik de Heuvel, Iwan J. P. de Esch, Tiffany van der Meer, Marco Siderius, Geert Jan Sterk, David Brown, Rob Leurs
Summary: This study investigated the potential of Schistosoma mansoni phosphodiesterase SmPDE4A as a new drug target for schistosomiasis. The researchers cloned, isolated, and characterized the full-length and catalytic domains of SmPDE4A. They found that SmPDE4A resembles human PDE4 more than parasite PDEs. Screening of PDE inhibitors identified tetrahydrophthalazinones and benzamides as potential hits, but further evaluation showed that the inhibitors were not effective against S. mansoni, suggesting that SmPDE4A is not a suitable target for anti-schistosomiasis therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Tom Dekker, Jaap W. W. Harteveld, Gabor Wagner, Max C. M. de Vries, Hans Custers, Andrea C. van de Stolpe, Iwan J. P. de Esch, Maikel Wijtmans
Summary: Biomass-derived molecules have the potential for sustainable drug discovery, but their exploration is hindered by the dominance of old-fashioned screening compounds in classical high-throughput screening libraries. We propose a fragment-based drug discovery approach as an efficient method to navigate biomass-derived drug space. In a proof-of-concept study using dihydrolevoglucosenone (Cyrene TM), we generated a diverse fragment library with good physicochemical properties and potential for novel drug candidates based on renewable resources.
Article
Multidisciplinary Sciences
Zhongxuan Ma, K. D. Augustijn, I. J. P. De Esch, B. A. G. Bossink
Summary: This study investigates the micro-foundations of dynamic capabilities in university technology transfer through qualitative case studies at two organizations. The micro-foundations of sensing include selecting internal competency and sensing external partners, while seizing involves resource co-allocation and collaborative business model. The micro-foundations of reconfiguring include strategic renewal, establishing a university technology transfer-friendly environment, and asset orchestration. This study provides better understanding of how dynamic capabilities facilitate university technology transfer, and offers suggestions for industrial practitioners and policymakers.
Article
Chemistry, Medicinal
Tom Dekker, Mathilde A. C. H. Janssen, Christina Sutherland, Rene W. M. Aben, Hans W. Scheeren, Daniel Blanco-Ania, Floris P. J. T. Rutjes, Maikel Wijtmans, Iwan J. P. de Esch
Summary: The success of fragment-based drug discovery (FBDD) is closely related to library design. A workflow in KNIME software has been created to guide the design of fragment libraries, considering chemical diversity and novelty of the fragments, as well as their three-dimensional (3D) character. This design tool can create large and diverse libraries or select representative compounds to enrich existing libraries.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biology
Matyas A. Bittenbinder, Nick D. Bergkamp, Julien Slagboom, Jan Paul M. Bebelman, Nicholas R. Casewell, Marco H. Siderius, Martine J. Smit, Jeroen Kool, Freek J. Vonk
Summary: Snakebite envenoming is a significant public health concern with high mortality rates. Snake venoms can have various harmful effects on the body, including tissue damage. This study presents a workflow using fluorescently labeled ECM components to investigate the degradation of ECM caused by snake venom. This approach provides valuable insights into the mechanisms of proteolytic venom components and could aid in the development of effective snakebite treatments.
Article
Chemistry, Medicinal
Icaro A. Simon, Evert J. Homan, Maikel Wijtmans, Michael Sundstrom, Rob Leurs, Iwan J. P. De Esch, Barbara A. Zarzycka
Summary: The researchers have developed an open-source computational platform, called PSW-Designer, for the design and screening of new photoswitchable ligands, especially for GPCRs. Through two case studies, they validate the predictive capabilities of the platform and anticipate that it will facilitate the design of improved photoswitchable molecules.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Chemistry, Physical
Michail Papadourakis, Hryhory Sinenka, Pierre Matricon, Jerome Henin, Grace Brannigan, Laura Perez-Benito, Vineet Pande, Herman van Vlijmen, Chris de Graaf, Francesca Deflorian, Gary Tresadern, Marco Cecchini, Zoe Cournia
Summary: This article reviews the progress in alchemical free energy calculations of membrane proteins, focusing on best practices and critical aspects of simulations on G-protein-coupled receptors, ion channels, transporters, and protein-lipid interactions. The study reveals the valuable application of alchemical free energy calculations in drug discovery for membrane-associated proteins.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Biochemistry & Molecular Biology
Nick D. Bergkamp, Jeffrey R. van Senten, Hendrik J. Brink, Maarten P. Bebelman, Jelle van den Bor, Tugce S. Cobanoglu, Kasper Dinkla, Johannes Koester, Gunnar Klau, Marco Siderius, Martine J. Smit
Summary: The G-protein coupled receptor US28 encoded by human cytomegalovirus (HCMV) is associated with accelerated progression of glioblastomas. In this study, it was found that US28 enhances signaling mediated by sphingosine-1-phosphate (S1P), promoting glioblastoma cell proliferation and survival. The study also uncovers the roles of S1P and CIP2A in US28-mediated exacerbation of glioblastoma.
Article
Multidisciplinary Sciences
Maarten P. Bebelman, Irfan M. Setiawan, Nick D. Bergkamp, Jeffrey R. van Senten, Caitrin Crudden, Jan Paul M. Bebelman, Frederik J. Verweij, Guillaume van Niel, Marco Siderius, D. Michiel Pegtel, Martine J. Smit
Summary: The HCMV-encoded chemokine receptor US28 plays a role in various aspects of the viral life cycle and immune evasion by scavenging chemokines from HCMV-infected cells. It localizes to late endosomal compartments called multivesicular bodies (MVBs) and can be secreted on exosomes through fusion with the plasma membrane. The exosomal release of US28 contributes to chemokine scavenging and immune evasion by HCMV.
Article
Biochemical Research Methods
Jelle van den Bor, Nick D. Bergkamp, Stephanie M. Anbuhl, Francoise Dekker, Dehan Comez, Claudia V. Perez Almeria, Reggie Bosma, Carl W. White, Laura E. Kilpatrick, Stephen J. Hill, Marco Siderius, Martine J. Smit, Raimond Heukers
Summary: The use of nanobodies and NanoBRET methods allows for real-time monitoring of nanobody-receptor binding, predicting the therapeutic potential of ligands targeting disease-associated membrane proteins, which is significant for drug research.
CELL REPORTS METHODS
(2023)
Letter
Oncology
Gamal A. Wakileh, Philipp Bierholz, Mara Kotthoff, Margaretha A. Skowron, Felix Bremmer, Alexa Stephan, Stephanie M. Anbuhl, Raimond Heukers, Martine J. Smit, Philipp Stroebel, Daniel Nettersheim
Summary: This study identified a nanobody-drug-conjugate targeting CXCR4 as a potential therapeutic option for GCT. Furthermore, this study shed light on the functional role of the CXCR4 / CXCR7 / CXCL12-signaling cascade in GCT, demonstrating an important influence on proliferation and migration.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
