Article
Environmental Sciences
Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Ilandarage Menu Neelaka Molagoda, Yung Hyun Choi, Sang Rul Park, Seungheon Lee, Gi-Young Kim
Summary: Low concentrations of BPA induce inflammation by activating the NF-kappa B signaling pathway and increasing the release of proinflammatory mediators. Molecular modeling suggests that BPA binds to the TLR4/MD2 complex to initiate downstream molecules and elicit an immune response.
ENVIRONMENTAL POLLUTION
(2021)
Article
Immunology
Wei Zhang, Eun-Koung An, Juyoung Hwang, Jun-O Jin
Summary: The study found that LPS can directly stimulate pDCs via the TLR4/MD2 pathway and promote the activation of pDCs and cDCs. cDCs may contribute to the enhancement of IFN-alpha production in pDCs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Thura Tun Oo, Natticha Sumneang, Benjamin Ongnok, Busarin Arunsak, Titikorn Chunchai, Sasiwan Kerdphoo, Nattayaporn Apaijai, Wasana Pratchayasakul, Guang Liang, Nipon Chattipakorn, Siriporn C. Chattipakorn
Summary: The study demonstrated that the MD-2 inhibitor L6H21 and metformin can attenuate metabolic disturbances and restore cognitive function in a model of prediabetes induced by high-fat diet.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Danieli F. Buccini, Beatriz C. Roriz, Julia M. Rodrigues, Octavio L. Franco
Summary: Antimicrobial peptides are important molecules in the organism's defense system. They can modulate the immune system and recognize molecules present in pathogens. Overstimulation of TLR4 can lead to uncontrolled inflammatory responses, which can be counteracted by antimicrobial peptides.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Colton D. Payne, Bastian Franke, Mark F. Fisher, Fatemeh Hajiaghaalipour, Courtney E. McAleese, Angela Song, Carl Eliasson, Jingjing Zhang, Achala S. Jayasena, Grishma Vadlamani, Richard J. Clark, Rodney F. Minchin, Joshua S. Mylne, K. Johan Rosengren
Summary: Head-to-tail cyclized peptides, such as PawS-Derived Peptides (PDPs), exhibit unique structures and properties, making them suitable for cell delivery and accessing novel targets. PDP-23 forms a dimeric structure in water, which can be split into monomers by addition of micelles or organic solvent, presenting different levels of hydrophobicity in open or closed V-shapes.
Review
Biochemical Research Methods
Anna Torkamannia, Yadollah Omidi, Reza Ferdousi
Summary: Combination pharmacotherapy with synergistic effect is an effective strategy for treating complex diseases, but testing different compound combinations is expensive and challenging. Computational methods, particularly machine learning algorithms, have achieved significant success in predicting synergistic drug combinations in cancer.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Lucia Perez-Regidor, Joan Guzman-Caldentey, Nils Oberhauser, Carmen Punzon, Balazs Balogh, Jose R. Pedro, Eva Falomir, Alessandra Nurisso, Peter Matyus, J. Carlos Menendez, Belen de Andres, Manuel Fresno, Sonsoles Martin-Santamaria
Summary: In this study, a computer-aided drug repurposing approach was used to virtually screen and discover novel TLR4 modulators with a non-lipopolysaccharide-like structure. After screening thousands of approved drugs and drug-like molecules, several compounds with TLR4 antagonist activity were identified through biological assays. This collaborative work expands the chemical diversity for the inspiration of new classes of TLR4 modulators.
Article
Hematology
Mina Noura, Ken Morita, Hiroki Kiyose, Yukiko Okuno, Hidemasa Matsuo, Asami Koyama, Yoko Nishinaka-Arai, Yasuhiko Kamikubo, Souichi Adachi
Summary: Differentiation therapy, specifically using albendazole to stimulate a differentiation axis, shows promise as a novel treatment for non-APL acute myeloid leukaemia (AML), with potential efficacy both in vitro and in vivo.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Chemistry, Applied
Alejandra Matamoros-Recio, Javier Merino, Alicia Gallego-Jimenez, Raquel Conde-Alvarez, Manuel Fresno, Sonsoles Martin-Santamaria
Summary: LPS plays a crucial role in bacterial infection and can be recognized by TLR4. The chemical structure of LPS affects its function and immune response. Computational techniques can help understand the interaction between TLR4 and atypical LPSs from opportunistic bacteria, providing insights into immune evasion mechanisms.
CARBOHYDRATE POLYMERS
(2023)
Review
Biochemistry & Molecular Biology
Oystein Bruserud, Hakon Reikvam, Annette Katharina Brenner
Summary: Toll-like receptor 4 (TLR4) is a pattern-recognizing receptor expressed by acute myeloid leukemia (AML) cells, bone marrow stromal cells, and nonleukemic cells involved in inflammation. It can bind a wide range of endogenous ligands present in the bone marrow microenvironment.
Article
Biochemistry & Molecular Biology
Shuo Wang, Hongshuang Wang, Cong Lin, Tianshu Zhang, Jingwei Gao, Siru Wu, Yibo Wang, Hongyuan Li, Weihong Min, Chunlei Liu, Xiaohui Wang
Summary: This study explores the structure-activity relationship of DHA derivatives as TLR4 antagonists, providing structural guidance for repositioning DHA derivatives as effective TLR4 antagonists.
BIOORGANIC CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Tahnee J. Dening, Justin T. Douglas, Michael J. Hageman
Summary: The study demonstrated the interactions between water-soluble peptide drugs and bile salts in the gastrointestinal tract, affecting peptide membrane flux and enzymatic stability.
MOLECULAR PHARMACEUTICS
(2021)
Article
Immunology
Wei Zhang, Li Xu, Xiaoyan Zhang, Jianqing Xu, Jun-O Jin
Summary: This study investigates the potential effect of FimH on macrophage polarization and activation. The results show that FimH promotes M1 macrophage activation and repolarizes M2 macrophages into the M1 phenotype via the TLR4 signaling pathway. Moreover, FimH reprograms tumor-associated macrophages in the tumor microenvironment and enhances the anti-tumor activity of immune checkpoint blockade.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell & Tissue Engineering
Marina Sanchez-Petidier, Consuelo Guerri, Victoria Moreno-Manzano
Summary: This study demonstrates the important role of Toll-like receptors (TLRs) in neural precursor cells (NPCs) of the spinal cord. TLRs play distinct regulatory roles in maintaining the self-renewal and cell differentiation of NPCs.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Oncology
Jiawen Yang, Qiaoliang Zhu, Yifan Wu, Xiaojuan Qu, Haixia Liu, Biao Jiang, Di Ge, Xiaoling Song
Summary: Protein-protein interactions play essential roles in cellular processes, and dysregulated PPIs are involved in various diseases, including cancer. Macrocyclic peptides, with features such as moderate sizes, high selectivity, and high binding affinities, have gained attention as potential therapeutic candidates for targeting dysregulated PPIs in cancer treatment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alisa Khramushin, Orly Marcu, Nawsad Alam, Orly Shimony, Dzmitry Padhorny, Emiliano Brini, Ken A. Dill, Sandor Vajda, Dima Kozakov, Ora Schueler-Furman
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2020)
Article
Biochemistry & Molecular Biology
Dzmitry Padhorny, Kathryn A. Porter, Mikhail Ignatov, Andrey Alekseenko, Dmitri Beglov, Sergei Kotelnikov, Ryota Ashizawa, Israel Desta, Nawsad Alam, Zhuyezi Sun, Emiliano Brini, Ken Dill, Ora Schueler-Furman, Sandor Vajda, Dima Kozakov
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2020)
Article
Chemistry, Multidisciplinary
Rambabu N. Reddi, Adi Rogel, Efrat Resnick, Ronen Gabizon, Pragati Kishore Prasad, Neta Gurwicz, Haim Barr, Ziv Shulman, Nir London
Summary: Chemical modifications of proteins can impact various aspects of protein function, but there are limited methods for site-specific labeling in cells. The CoLDR strategy presented in this study allows for the installation of functional tags on target proteins while preserving their activity, enabling a wide range of applications. This approach, which includes labeling various proteins and assessing protein activity in a native environment, contributes to the tools available in chemical biology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Tomer Tsaban, Julia K. Varga, Orly Avraham, Ziv Ben-Aharon, Alisa Khramushin, Ora Schueler-Furman
Summary: Highly accurate protein structure predictions by deep neural networks such as AlphaFold2 and RoseTTAFold have great impact on structural biology and beyond. This study demonstrates that AlphaFold2 can also be used for quick and accurate modeling of peptide-protein interactions. The results highlight the potential of AlphaFold2 in providing structural insight into a wide range of peptide-protein complexes.
NATURE COMMUNICATIONS
(2022)
Article
Urology & Nephrology
Alia Hassan, Yael E. E. Pollak, Rachel Kilav-Levin, Justin Silver, Nir London, Morris Nechama, Iddo Z. Z. Ben-Dov, Tally Naveh-Many
Summary: This study reveals that kidney failure leads to the loss of Pin1 activity in the parathyroid glands, resulting in increased production of PTH. Pin1 and KSRP phosphorylation, as well as the Pin1-KSRP-PTH mRNA axis, play important roles in secondary hyperparathyroidism.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Chemistry, Multidisciplinary
Roeland Vanhoutte, Marta Barniol-Xicota, Winston Chiu, Laura Vangeel, Dirk Jochmans, Steven De Jonghe, Hadeer Zidane, Haim M. Barr, Nir London, Johan Neyts, Steven H. L. Verhelst
Summary: The vulnerability of the modern society has been exposed by the COVID-19 pandemic, and it is crucial to have effective treatment options for infected individuals. We have designed a solid-phase synthesis route to create azapeptide activity-based probes for the SARS-CoV-2 main protease, which have shown to be potent inhibitors. These probes can be used to visualize the activity of the protease and the engagement of drugs in infected cells.
Editorial Material
Chemistry, Multidisciplinary
Julia K. Varga, Ora Schueler-Furman
Summary: Deep learning, led by DeepMind's Alphafold2, has brought revolutionary breakthroughs in structural biology, allowing generation of high-quality structural models for most known proteins and protein interactions. The next challenge is to utilize these models to understand protein binding, including partner identification and affinity. Chang and Perez propose an elegant approach, focusing on interactions involving short peptides and their receptors, where presenting both peptides to the receptor simultaneously allows Alphafold2 to predict the tighter binding peptide at the binding site. This simple yet effective idea demonstrates promising results.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Sayanika Banerjee, Julia K. Varga, Manoj Kumar, Guy Zoltsman, Shahar Rotem-Bamberger, Einav Cohen-Kfir, Michail N. Isupov, Rina Rosenzweig, Ora Schueler-Furman, Reuven Wiener
Summary: This study comprehensively investigates the activity of UFL1, its interaction with UFC1, and its relation to UBA5, revealing a novel regulatory mechanism.
Article
Chemistry, Multidisciplinary
Daniel S. Bejan, Sunil Sundalam, Haihong Jin, Rory K. Morgan, Ilsa T. Kirby, Ivan R. Siordia, Barr Tivon, Nir London, Michael S. Cohen
Summary: PARP16, a potential therapeutic target for cancer treatment, has poorly understood catalytic activity. This study describes the design of a selective PARP16 inhibitor and reveals that the catalytic activity of PARP16 regulates its solubility in response to nutrient stress.
Article
Genetics & Heredity
Tomer Tsaban, Doron Stupp, Dana Sherill-Rofe, Idit Bloch, Elad Sharon, Ora Schueler-Furman, Reuven Wiener, Yuval Tabach
Summary: Mapping co-evolved genes through phylogenetic profiling can reveal functional interactions and pathways in eukaryotes. By analyzing different clades, we found that functionally related genes exhibit distinct co-evolution patterns, highlighting the importance of modular co-evolution analysis. Our 'CladeOScope' method integrates information from multiple clades and genomes and can be accessed through a user-friendly web server.
NAR GENOMICS AND BIOINFORMATICS
(2021)
Article
Chemistry, Multidisciplinary
Barr Tivon, Ronen Gabizon, Bente A. Somsen, Peter J. Cossar, Christian Ottmann, Nir London
Summary: The study introduces a computational pipeline, Rosetta CovPepDock, for successful docking of peptides with irreversible covalent bonds to protein receptors. Retrospective experiments showed a high success rate of 89% and 100% when docking from the native conformation. Additionally, by designing based on known non-covalent binders or protein-protein interfaces, the pipeline validated seven highly potent and selective irreversible peptide binders.
Article
Chemistry, Multidisciplinary
Aaron Morris, William McCorkindale, Nir Drayman, John D. Chodera, Savas Tay, Nir London, Alpha A. Lee
Summary: The research team used machine learning for novel compound design and synthesis route prediction, successfully identifying chemical scaffolds with antiviral activity. These findings are significant for the development of patent-free antiviral drugs.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jingxu Guo, Alice Douangamath, Weixiao Song, Alun R. Coker, A. W. Edith Chan, Steve P. Wood, Jonathan B. Cooper, Efrat Resnick, Nir London, Frank von Delft
JOURNAL OF STRUCTURAL BIOLOGY-X
(2020)
Article
Chemistry, Medicinal
Yuka Murakawa, Shirly Valter, Haim Barr, Nir London, Takayoshi Kinoshita
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Multidisciplinary Sciences
Ofrah Faust, Meital Abayev-Avraham, Anne S. Wentink, Michael Maurer, Nadinath B. Nillegoda, Nir London, Bernd Bukau, Rina Rosenzweig
Article
Chemistry, Organic
Fuying Zhu, Yamei Lin
Summary: In this study, a low-metal iron-supported catalyst (Fe20/NC-Mg) was reported for the efficient synthesis of quinoxaline compounds, using water as a solvent and without additional bases. The synergistic effect of FeNx site and Mg (OH)2 nanorods in the catalyst played a key role in achieving high yields (82-91%) in 16 examples. The gram-level synthesis and reusability of the catalysts after four cycles demonstrated its industrial application potential.
Article
Chemistry, Organic
Mikhail Kozlov, Alexey Tyurin, Andrey Dmitrenok, Vyacheslav Rusak, Aleksander Fedorov, Igor Zavarzin, Yulia Volkova
Summary: This study presents a novel and practical synthesis method for phosphorus-substituted 1,3,4-thiadiazolines using phosphorylthioformic acid hydrazides and ketones. The protocol demonstrates operational simplicity, availability of reagents, and tolerance towards different functional groups.
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.
