Article
Biochemistry & Molecular Biology
Yueyue Zhu, Bo Liu, Zonglong Chen, Xianyang Wang, Yujie Wang, Wenhong Zhang, Sen Wang, Mingming Zhang, Yingxia Li
Summary: Through structural modifications of TLR2 agonists, we have obtained a highly specific agonist 14a with powerful immunostimulatory activity, which can induce immune cells to produce inflammatory cytokines and trigger signaling pathways. This makes 14a a potential candidate for immunostimulants.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Minagi Mukaiyama, Chihiro Uchiyama, Akane Fukuda, Yoshiki Nakazawa, Yuka Kuramochi, Yudai Shibata, Sho Konno, Kyohei Muguruma, Naohiro Matsugaki, Tomo Asari, Kazuyoshi Ogawa, Akihiro Taguchi, Kentaro Takayama, Atsuhiko Taniguchi, Yoko Nagumo, Toshiya Senda, Yoshio Hayashi, Takeo Usui
Summary: MA026, a cyclic lipodepsipeptide, opens tight junctions by binding to claudin-1. In this study, it was found that the amino acid sequence order at Glu10-Leu11 is important for the TJ-opening activity of MA026. Additionally, the epimers at the C3 position of the N-terminal acyl tail showed decreased TJ-opening activity. The three-dimensional structure and systematic structure-activity relationship study of MA026 revealed that the hydrophobic region is crucial for its TJ-opening activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Environmental Sciences
John D. Hansen, Keith A. Loftin, Zachary Laughrey, Ondrej Adamovsky
Summary: Various stressors can have profound impacts on immunity to pathogens, with little research into the effects of cyanobacterial toxins on disease resistance in mammals. Recent studies suggest that freshwater cyanotoxins may alter disease susceptibility parameters for fish, wildlife, and human health through interaction with specific components of innate immunity. However, the results of this study indicate that the tested toxins did not directly interact with key pathogen recognition receptors for innate immunity in humans.
Review
Cell Biology
Elise E. Bruning, Janet K. Coller, Hannah R. Wardill, Joanne M. Bowen
Summary: TLR4 is a highly conserved protein involved in innate immunity with distinct roles in epithelial and immune cells throughout the gastrointestinal tract. While epithelial cell expression of TLR4 contributes to maintaining homeostasis, promoting immunoglobulin A production, and regulating permeability, immune cell expression is centered on maturation of dendritic cells and priming the adaptive immune system. However, further research is needed to fully understand the impact of site-specific TLR4 expression on inflammation and disease progression.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Obstetrics & Gynecology
Wedad S. Aboussahoud, Helen Smith, Adam Stevens, Ivan Wangsaputra, Helen R. Hunter, Susan J. Kimber, Mourad W. Seif, Daniel R. Brison
Summary: The study found that pattern recognition receptors and Toll-like receptor genes are widely expressed in early human embryos, suggesting the activation of the innate immunity system during embryo development. Understanding the role of the Toll-like receptor system in preimplantation human development may provide insights into immunological mechanisms and potential clinical markers of embryo quality and pregnancy initiation.
HUMAN REPRODUCTION
(2021)
Review
Medicine, Research & Experimental
Jinrui Wei, Yan Zhang, Haopeng Li, Fuquan Wang, Shanglong Yao
Summary: This review focuses on the role and mechanism of TLR4 in various diseases, aiming to provide new research directions and therapeutic targets for clinical intervention.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Endocrinology & Metabolism
Hai-Yun Guan, He-Xia Xia, Xiu-Ying Chen, Lu Wang, Zhi-Jing Tang, Wei Zhang
Summary: The activation of TLR4 was found to suppress CYP19A1 expression and E2 secretion in human granulosa cells via NF-κB signaling, which has implications for follicular development and estrogen synthesis regulation.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Cell Biology
Patrick Thon, Katharina Rump, Annika Knorr, Birte Dyck, Dominik Ziehe, Matthias Unterberg, Hartmuth Nowak, Lars Bergmann, Alexander Wolf, Maha Bazzi, Jennifer Orlowski, Marcus Peters, Alexander Zarbock, Thorsten Brenner, Michael Adamzik, Tim Rahmel, Bjoern Koos
Summary: We established a diagnostic assay to quantify the phosphorylation of TLR-4, which can be used in both cell culture and clinical samples of sepsis patients, enabling large-scale stratification of sepsis patients based on their TLR-4 activation status.
Review
Immunology
Xin Zheng, Song Li, Hui Yang
Summary: TLR3 is an important member of the TLR family that can recognize double-stranded RNA and play a role in immune responses, and it has also been detected in some tumors. TLR3 may play protumor or antitumor roles in different tumors.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Niloofar Deravi, Mohadeseh Poudineh, Marzieh Pirzadeh, Hanie Yavarpour-Bali, Hoda Mehrabi, Gisou Erabi, Amene Saghazadeh, Nima Rezaei
Summary: Endothelial cells play a critical role in innate immune and inflammatory responses, and Toll-like receptors (TLRs) are key in activating innate mechanisms in ECs. Endothelial dysfunction may lead to tissue damage in various diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eunjeong Lee, Jasmina S. Redzic, Travis Nemkov, Anthony J. Saviola, Monika Dzieciatkowska, Kirk C. Hansen, Angelo D'Alessandro, Charles Dinarello, Elan Z. Eisenmesser
Summary: This study used a combination of biophysical and biochemical methods to investigate the dynamic behavior and functional interactions of bacterial TIR-containing proteins and mammalian receptor TIR domains. The findings highlight the differences in dynamics and functionality between bacterial and mammalian TIR domains, as well as the variations in oligomeric interactions.
Review
Critical Care Medicine
Sahil Gupta, James N. Tsoporis, Song-Hui Jia, Claudia C. dos Santos, Thomas G. Parker, John C. Marshall
Summary: This article discusses how host cells recognize danger signals using pattern recognition receptors, focusing on Toll-like receptors (TLRs) as the most studied class of PRRs. It reviews the expression, regulation, and function of different TLRs, emphasizing TLR-4, and how TLR adaptor protein binding directs intracellular signaling to activate or terminate an innate immune response. The recent progress in research on the involvement of S100 proteins as ligands for TLR-4 in inflammatory disease is also highlighted.
Article
Immunology
Stine Sofie Frank Lende, Marie Host Pahus, Ida Monrad, Rikke Olesen, Anna R. Mahr, Line K. Vibholm, Lars Ostergaard, Ole Schmeltz Sogaard, Anna Halling Folkmar Andersen, Paul W. Denton, Martin Tolstrup
Summary: This study investigates the potential of CD169 expression on monocytes as a biomarker for innate immunity activation in cancer and viral infection treatment. Through ex vivo experiments, animal models, and clinical trials, the researchers found that an increase in the percentage of CD169 positive monocytes is a reliable biomarker for immune activation following TLR9 agonist treatment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kwadwo A. Opoku-Nsiah, Andres H. de la Pena, Sarah K. Williams, Nikita Chopra, Andrej Sali, Gabriel C. Lander, Jason E. Gestwicki
Summary: The study reveals the sequence preferences and gate-opening mechanisms of the human 20S proteasome (h20S). It shows that the recognition sequence of h20S is different from the archaeal system and is defined as the Y-F/Y (Y Phi) motif. The Y Phi sequence preferences can be tuned by valency, allowing multivalent proteasome activators to explore a greater sequence space. These findings expand the understanding of termini-mediated gating and provide insights for the design of h20S activators.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Malgorzata Sobstyl, Paulina Niedzwiedzka-Rystwej, Rafal Hrynkiewicz, Dominika Bebnowska, Izabela Korona-Glowniak, Marcin Pasiarski, Barbara Sosnowska-Pasiarska, Jolanta Smok-Kalwat, Stanislaw Gozdz, Anna Sobstyl, Wojciech Polkowski, Jacek Rolinski, Ewelina Grywalska
Summary: The study demonstrated the significance of TLR2 as a biomarker in advanced stage ovarian cancer by showing significantly higher expression levels in women with more advanced OC. This research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and increasing survival in confirmed ovarian cancer patients.
Article
Public, Environmental & Occupational Health
Sara Hanaei, Amirhossein Takian, Reza Majdzadeh, Christopher Ryan Maboloc, Igor Grossmann, Orlando Gomes, Milos Milosevic, Manoj Gupta, Alireza A. Shamshirsaz, Amine Harbi, Amer M. Burhan, Lucina Q. Uddin, Arutha Kulasinghe, Chi-Ming Lam, Seeram Ramakrishna, Abass Alavi, Jan L. Nouwen, Tommaso Dorigo, Michael Schreiber, Ajith Abraham, Natalya Shelkovaya, Wojtek Krysztofiak, Majid Ebrahimi Warkiani, Frank Sellke, Shuji Ogino, Francisco J. Barba, Serge Brand, Clara Vasconcelos, Deepak B. Salunke, Nima Rezaei
Summary: The COVID-19 pandemic has had a significant impact on human life, leading to the postponement, cancellation, or virtualization of activities that require gatherings. While virtual settings offer increased inclusivity and accessibility and reduce carbon emissions, they cannot fully replace in-person scientific events. In-person meetings allow for socialization, collaboration, and idea sharing, providing novel opportunities. A hybrid model that combines in-person and virtual components may be a solution, allowing participants to choose their preferred mode of participation.
DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS
(2022)
Article
Chemistry, Medicinal
Arshpreet Kaur, Deepender Kaushik, Sakshi Piplani, Surinder K. Mehta, Nikolai Petrovsky, Deepak B. Salunke
Summary: Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) in microbial species. Among them, TLR2 stands out for its ability to heterodimerize with TLR1 or TLR6, allowing it to sense a wide range of PAMPs. Various scaffolds, including lipoproteins and lipopeptides, can activate TLR2, with approaches such as lipidation of antigens or conjugation to polymers used for delivering TLR2 agonists effectively. Structural features that facilitate TLR2 activation include crystal structure analysis and computational modeling.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Rahul Singh, Ravinder Kumar, Mallesh Pandrala, Parleen Kaur, Saloni Gupta, Dhanir Tailor, Sanjay Malhotra, Deepak B. Salunke
Summary: This study synthesized a series of C6-substituted benzimidazo[1,2-a]quinoxaline derivatives and evaluated their anticancer activity in the NCI-60 cancer cell lines. The substituents were found to play a significant role in the activity, with indole, imidazole, and benzimidazole derivatives showing significant activity against triple-negative breast cancer cell lines.
ARCHIV DER PHARMAZIE
(2021)
Article
Chemistry, Medicinal
Hong-Rae Kim, Ravichandra Tagirasa, Euna Yoo
Summary: Cells of the immune system use proteases to regulate functions and immune responses, with dysregulated activities linked to disorders. Compounds that modify protease active sites covalently are emerging as important drugs, serving as both chemical probes and approved agents for pharmaceutical development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Kevin J. Frankowski, Tarsis Brust, Kimberly M. Lovell, Euna Yoo, Laura M. Bohn, Jeffrey Aube
Summary: By investigating the structure-activity relationship effects for all three functional groups attached to the triazole core, specific groups critical for KOR potency were identified, leading to the discovery of analogs with potency on par with the lead triazole probe molecule, as well as analogs possessing less potent KOR agonist activity.
MEDICINAL CHEMISTRY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yihang Jing, Sarah E. Bergholtz, Anthony Omole, Rhushi A. Kulkarni, Thomas T. Zengeya, Euna Yoo, Jordan L. Meier
Summary: This study presents a new chemical strategy for synthesizing a stable isostere of malonyllysine, which can mimic features of endogenous lysine modification and be used for tool development and functional analysis. The isostere shows resistance to thermal decarboxylation and can be recognized by anti-malonyllysine antibodies and histone deacylases.
Article
Chemistry, Organic
Rahul Singh, Ravinder Kumar, Manpreet Kaur, Madhuri T. Patil, Subash Chandra Sahoo, Deepak B. Salunke
Summary: A diverse library of fused tetracyclic and pentacyclic imidazo[4,5-b]pyridine scaffolds has been synthesized using an unconventional strategy involving Groebke-Blackburn-Bienayme multicomponent reaction and Pictet-Spengler cyclization. The structures of the synthesized polycyclic heterocycles were confirmed by various spectroscopic techniques and one of the library members was characterized using single-crystal X-ray diffraction.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Manpreet Kaur, Rahul Singh, Madhuri T. Patil, Kushvinder Kumar, Subash Chandra Sahoo, Kamal Nain Singh, Vinod D. Chaudhari, Deepak B. Salunke
Summary: A one-pot methodology was developed for the direct conversion of N-formylamine, 2-amino pyridine, and aldehyde into 2,3-substituted imidazo[1,2-a]pyridine heterocycles using I2-PPh3-Et3N reagent system under microwave irradiation. The study showcased the feasibility of this method, eliminating a separate step for the synthesis of isocyanides during the preparation of N-formylamines.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2022)
Review
Immunology
Ravichandra Tagirasa, Euna Yoo
Summary: The interaction between tumor and stroma during tumor development plays a crucial role in tumor progression, therapy, and immune response. Proteolytic enzymes, particularly serine proteases, expressed by tumor and stromal cells, are important in modulating tumor-stroma interaction. This review highlights the role of stromal-derived serine proteases in tumor progression and their potential therapeutic applications.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jyoti Rathee, Rohini Kanwar, Laxmi Kumari, Sandip Pawar, Shikha Sharma, Md Ehesan Ali, Deepak B. Salunke, Surinder Kumar Mehta
Summary: The aim of this study is to fabricate stable nanostructured lipid carriers (NLCs) using biocompatible excipients for encapsulating Methotrexate (MTX), a chemotherapeutic agent for breast cancer treatment. The prepared NLCs exhibited long-term stability and spherical shape morphology. The encapsulation efficiency of MTX reached around 85% and sustained release of MTX was achieved within 24 hours. Classical molecular dynamics simulations demonstrated the structural stability of the MTX-loaded NLCs. Hemolysis tests and MTT assays confirmed the biosafety and toxicity of the MTX-loaded NLCs, respectively.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Editorial Material
Pharmacology & Pharmacy
Arghya Ganguly, Euna Yoo
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
David P. P. Byun, Jennifer Ritchie, Yejin Jung, Ronald Holewinski, Hong-Rae Kim, Ravichandra Tagirasa, Joseph Ivanic, Claire M. M. Weekley, Michael W. W. Parker, Thorkell Andresson, Euna Yoo
Summary: This study defines the reactivity and selectivity of a set of BDHI-functionalized chemical fragments on cysteines using chemoproteomic profiling methods. The study demonstrates that BDHIs can react with reactive cysteine residues in the human proteome and their selectivity differs from that of haloacetamide electrophiles. Furthermore, BDHI forms covalent conjugates with potential anticancer targets and is used in the design of a BTK inhibitor.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Multidisciplinary
Muhammad Kazim, Euna Yoo
Summary: In the past two decades, there has been a significant revolution in tumor immunology, with clinical progress in various immunotherapy strategies. These advancements have highlighted the potential of harnessing the immune system to fight against cancer. However, the complex and heterogeneous nature of tumors and immune responses result in varying patient responses, emphasizing the need for reliable biomarkers and therapeutic strategies to maximize the benefits of immunotherapy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Editorial Material
Chemistry, Medicinal
Deepak B. Salunke, Craig W. Lindsley
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Chemistry, Medicinal
Deepak B. Salunke, Craig W. Lindsley
ACS MEDICINAL CHEMISTRY LETTERS
(2023)