Article
Immunology
Neamati Foroogh, Moniri Rezvan, Khorshidi Ahmad, Saffari Mahmood
Summary: This study is the first brief and effective review of issues related to the fimH adhesin, focusing on its structure, conformational changes, and potential applications in novel treatments for urinary tract infections.
MICROBIAL PATHOGENESIS
(2021)
Editorial Material
Pharmacology & Pharmacy
Peter J. Barnes
Summary: A recent study reveals the role of CCR1 in eosinophilic inflammation and the increased levels of its ligand CCL15 in asthmatic eosinophils. Another study demonstrates that N-truncated forms of CCL15 generated by tissue proteases induce biased CCR1 signaling. These findings may contribute to the development of more effective oral therapy for asthma by producing CCR antagonists.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Cleiment Gonnot, Mathieu Scalabrini, Benoit Roubinet, Ceilia Ziane, Fabien Boeda, David Deniaud, Ludovic Landemarre, Seibastien G. Gouin, Laurent Fontaine, Veironique Montembault
Summary: Well-defined, highly reactive poly(norbornenyl azlactone)s were synthesized by ring-opening metathesis polymerization (ROMP) of pure exo-norbornenyl azlactone with controlled length. Postpolymerization modification (PPM) strategy based on click aminolysis of azlactone side groups was employed to convert them into glycopolymers using pegylated mannoside, heptyl-mannoside, and pegylated glucoside. The resulting glycopolymers showed strong binding inhibition against lectins, surpassing the inhibitory potential of their monovalent analogues by four to five orders of magnitude.
Article
Multidisciplinary Sciences
Stone Woo, Ryan A. Shenvi
Summary: The ingestion of alkaloid metabolites from the bark of Galbulimima tree can lead to psychotropic and excitatory effects in humans. However, the limited supply of these alkaloids has hindered their exploration and development. In this study, researchers report a solution to the supply problem of GB18, a unique compound found in Galbulimima bark that is believed to have psychotropic effects. By developing new chemical reactions, the researchers were able to synthesize a large amount of GB18 and found it to be a potent antagonist of kappa- and mu-opioid receptors. This discovery opens up new possibilities for understanding the biological activity of Galbulimima metabolites.
Article
Chemistry, Medicinal
Xiangping Deng, Xiaofei Deng, Wentao Ning, Lilan Xin, Qiuzi Li, Zhiye Hu, Baohua Xie, Kaiwei Liang, Chang Min, Chune Dong, Jian Huang, Hai-Bing Zhou
Summary: Novel dual-functional ER & alpha; degraders were developed, which exhibited potent antiproliferative and ER & alpha; degradation activity, providing guidance for developing new antitumor drug candidates for ER & alpha;(+) breast cancer therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Leila Mousavifar, Meysam Sarshar, Clarisse Bridot, Daniela Scribano, Cecilia Ambrosi, Anna Teresa Palamara, Gerard Vergoten, Benoit Roubinet, Ludovic Landemarre, Julie Bouckaert, Rene Roy
Summary: A small library of FimH antagonists based on previously described C-linked allyl alpha-D-mannopyranoside was synthesized. Two new members with sub nanomolar affinity were identified and shown to have improved binding compared to previously published analogs. The crystal structure of FimH co-crystallized with one of the antagonists revealed its binding mode, and the antagonists were effective in decreasing bacterial adhesion to human bladder epithelial cells.
Review
Chemistry, Multidisciplinary
Zhengwei Liu, Mengyu Sun, Wenting Zhang, Jinsong Ren, Xiaogang Qu
Summary: Bioorthogonal chemistry is a promising tool for studying biological processes in their natural environment. Recent research has focused on its potential in medical treatment, as it allows in situ drug synthesis for improved efficacy and reduced side effects. This minireview highlights the design and development of targeted bioorthogonal reactions for precise medical treatment, providing strategies for achieving target-specific reactions and emphasizing their application for different therapeutic targets.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Katarzyna Bednarska-Szczepaniak, Adam Mieczkowski, Aleksandra Kierozalska, Dijana Pavlovic Saftic, Konrad Glabala, Tomasz Przygodzki, Lidia Stanczyk, Kamil Karolczak, Cezary Watala, Harsha Rao, Zhan-Guo Gao, Kenneth A. Jacobson, Zbigniew J. Lesnikowski
Summary: A series of adenosine and 2'-deoxyadenosine pairs modified with a boron cluster or phenyl group showed a general tendency to preferentially bind to the A(3) adenosine receptor. Boron cluster-modified ligands exhibited higher A(3) receptor selectivity compared to phenyl analogs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Agriculture, Multidisciplinary
Qiong Lu, Huijie Xie, Mingbo Qu, Tian Liu, Qing Yang
Summary: Sustainable agriculture requires selective insecticides, and the discovery of lepidopteran-specific molecular targets, such as the chitinase enzyme, can aid in the development of such insecticides. By understanding the biological function and crystal structure of the enzyme, as well as identifying small-molecule inhibitors, researchers have made progress in developing selective insecticides that are effective against lepidopteran pests but harmless to their natural enemies.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Microbiology
Gregoire Chevalier, Arnaud Laveissiere, Guillaume Desachy, Nicolas Barnich, Adeline Sivignon, Marc Maresca, Cendrine Nicoletti, Eric Di Pasquale, Margarita Martinez-Medina, Kenneth William Simpson, Vijay Yajnik, Harry Sokol, Temitayo Adegbamigbe, Tariq Ahmad, Ian Arnott, Yoram Bouhnik, Franck Carbonnel, Jean-Frederic Colombel, Glen Doherty, J. R. Fraser Cummings, Xavier Hebuterne, Hans Herfarth, David Kevans, Guillaume Pineton de Chambrun, Maria Nachury, Stephane Nancey, Xavier Roblin, Mark A. W. Tremelling, Jonathan Plassais, Francesco Strozzi, Alessandra Cervino, Rachel Morra, Christophe Bonny
Summary: The study identified a significant enrichment of FimH-expressing bacteria in the gut microbiome of CD patients, with FimH playing a crucial role in adhesion and inflammation induction. The specific FimH-blocker TAK-018 was shown to prevent bacterial adhesion and inflammation, potentially offering a promising treatment option for CD patients.
Article
Biochemistry & Molecular Biology
Kumaravel Mohankumar, Rupesh Shrestha, Stephen Safe
Summary: The study revealed that PSPC1 is crucial in cancer cells, with NR4A1 acting as a key regulator of PSPC1. NR4A1 antagonists inhibit tumor growth by downregulating PSPC1 and suppressing pro-oncogenic activities.
MOLECULAR CARCINOGENESIS
(2022)
Review
Pharmacology & Pharmacy
Leila Mousavifar, Rene Roy
Summary: Glycomimetics that mimic complex carbohydrate structures show potential in pathological processes and combatting antibiotic-resistant Escherichia coli infections. Advances in the synthesis of this compound family have been made, with one already in clinical trials for treating Crohn's disease, offering new hope for alternative antibacterial strategies.
DRUG DISCOVERY TODAY
(2021)
Review
Chemistry, Medicinal
Yijun Liu, Xin Lu, Nan Qin, Yuting Qiao, Shuaishuai Xing, Wenyuan Liu, Feng Feng, Zongliang Liu, Haopeng Sun
Summary: STING is a crucial player in the human innate immune system, activating production of interferons and cytokines to combat infections, inflammation, and tumorigenesis. Research focuses on STING's structure, function, regulation, and small molecule modulators for potential therapeutic applications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Marion Mathelie-Guinlet, Felipe Viela, David Alsteens, Yves F. Dufrene
Summary: Physical forces play a significant role in bacterial cell physiology and disease, particularly in the formation of catch-bonds under mechanical stress. While E. coli FimH adhesin has been the most studied microbial catch-bond, recent research indicates that proteins from other species, like staphylococci, also engage in stress-dependent interactions.
TRENDS IN MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Tianduanyi Wang, Otto I. Pulkkinen, Tero Aittokallio
Summary: Most drug molecules have the ability to modulate multiple target proteins, which can lead to both therapeutic effects and unwanted side effects. Evaluating the selectivity of a compound is an important factor in drug development and repurposing efforts. Traditional methods for characterizing selectivity fall short in quantifying how selective a compound is against a particular target protein. In this study, we propose an optimization-based selectivity scoring method that allows for the identification of potent and selective compounds against given kinase targets. We demonstrate the effectiveness of this method in finding highly selective compounds in computational experiments using a large-scale kinase inhibitor dataset.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Blijke S. Kroezen, Gabriele Conti, Benedetta Girardi, Jonathan Cramer, Xiaohua Jiang, Said Rabbani, Jennifer Mueller, Maja Kokot, Enrico Luisoni, Daniel Ricklin, Oliver Schwardt, Beat Ernst
Article
Chemistry, Medicinal
Tihomir Tomasic, Said Rabbani, Roman P. Jakob, Andreas Reisner, Ziga Jakopin, Timm Maier, Beat Ernst, Marko Anderluh
Summary: Bacterial resistance poses a significant challenge in treating urinary tract infections, and targeting the lectin FimH of uropathogenic E. coli with antiadhesive methods may be a promising approach. A novel series of FimH antagonists based on the 1-(alpha-D-mannopyranosyl)-4-phenyl-1,2,3-triazole scaffold have shown improved binding affinities, suggesting potential new strategies for combating bacterial resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jonathan Cramer, Butrint Aliu, Xiaohua Jiang, Timothy Sharpe, Lijuan Pang, Adrian Hadorn, Said Rabbani, Beat Ernst
Summary: Research has shown that mannose-functionalized poly-L-lysine glycoconjugates efficiently inhibit viral attachment and prevent virus binding to DC-SIGN receptors. After treatment, these polymers can lead to prolonged receptor internalization and inhibition of virus binding for up to 6 hours.
Article
Chemistry, Multidisciplinary
Oliver Schwardt, Christina Lamers, Clement Bechtler, Daniel Ricklin
Summary: Peptides have become a particularly attractive option for academic drug discovery and development due to their modular structure, extendibility, availability of screening platforms, and ease-of-synthesis. The Molecular Pharmacy group at the University of Basel focuses on the therapeutic modulation of host defense pathways using peptides, introducing students to practical aspects of drug design and discovering novel therapeutics for immune and inflammatory diseases. The versatile and promising nature of peptide-based drugs has created a perfect circle between pharmaceutical research and education, with recent clinical applications increasing their value and relevance.
Article
Chemistry, Medicinal
Benedetta Girardi, Martina Manna, Sjors Van Klaveren, Tihomir Tomasic, Ziga Jakopin, Hakon Leffler, Ulf J. Nilsson, Daniel Ricklin, Janez Mravljak, Oliver Schwardt, Marko Anderluh
Summary: The study aimed to improve the affinity and target selectivity of a galectin-8 ligand by introducing modifications at positions 1 and 3 of the galactose, resulting in a promising lead for the development of new selective and potent ligands for galectin-8, highlighting its potential role in cell-based and in vivo studies.
Article
Chemistry, Medicinal
Philipp Daetwyler, Xiaohua Jiang, Beatrice Wagner, Norbert Varga, Tobias Muehlethaler, Katja Hostettler, Said Rabbani, Oliver Schwardt, Beat Ernst
Summary: The conversion of carbohydrates into ester prodrugs can improve oral availability but may also lead to issues such as oxidation and efflux. Therefore, different modifications of carbohydrates need to be studied comprehensively for their effects.
Article
Chemistry, Multidisciplinary
Robert Wawrzinek, Eike-Christian Wamhoff, Jonathan Lefebre, Mareike Rentzsch, Gunnar Bachem, Gary Domeniconi, Jessica Schulze, Felix F. Fuchsberger, Hengxi Zhang, Carlos Modenutti, Lennart Schnirch, Marcelo A. Marti, Oliver Schwardt, Maria Braeutigam, Monica Guberman, Dirk Hauck, Peter H. Seeberger, Oliver Seitz, Alexander Titz, Beat Ernst, Christoph Rademacher
Summary: Dendritic cells play a crucial role in coordinating immune responses, with new research showing potential for improved targeting of specific dendritic cell subtypes. This discovery has important implications for immunotherapy and anti-infectives.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Jonathan Cramer, Adem Lakkaichi, Butrint Aliu, Roman P. Jakob, Sebastian Klein, Ivan Cattaneo, Xiaohua Jiang, Said Rabbani, Oliver Schwardt, Gert Zimmer, Matias Ciancaglini, Tiago Abreu Mota, Timm Maier, Beat Ernst
Summary: DC-SIGN is a pattern recognition receptor implicated in virus dissemination and innate immune response stimulation, making it a potential target for host-directed strategies to attenuate the progression of viral infections. The discovery of potent glycomimetic ligands with improved binding affinity provides promising prospects for the development of targeted therapeutics against a broad spectrum of viral infections.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Tiago Bozzola, Mariafrancesca Scalise, Christer U. Larsson, Michael C. Newton-Vesty, Caterina Rovegno, Ankita Mitra, Jonathan Cramer, Weixiao Yuan Wahlgren, Partha Radhakrishnan Santhakumari, Richard E. Johnsson, Oliver Schwardt, Beat Ernst, Rosmarie Friemann, Renwick C. J. Dobson, Cesare Indiveri, Jenny Schelin, Ulf J. Nilsson, Ulf Ellervik
Summary: This study presents the development of novel drugs that can inhibit the bacterial sialic acid symporter SiaT. Through the use of structure-based drug design and synthesis, the researchers were able to create compounds with significantly higher affinity compared to natural substrates. These compounds effectively delayed bacterial growth in methicillin-resistant Staphylococcus aureus, suggesting their potential as new antibacterial agents.
ACS CHEMICAL BIOLOGY
(2022)
Article
Engineering, Biomedical
Clement Bechtler, Sophia Koutsogiannaki, Ekaterina Umnyakova, Amal Hamid, Avneesh Gautam, Yiannis Sarigiannis, Richard B. Pouw, Christina Lamers, Said Rabbani, Christoph Q. Schmidt, John D. Lambris, Daniel Ricklin
Summary: The use of biomaterials in modern medicine has advanced drug delivery strategies and reduced morbidity and mortality. However, immune reactions remain a serious complication.
ACTA BIOMATERIALIA
(2023)
Article
Biochemistry & Molecular Biology
Beatrice Wagner, Florian P. C. Binder, Xiaohua Jiang, Tobias Muhlethaler, Roland C. Preston, Said Rabbani, Martin Smiesko, Oliver Schwardt, Beat Ernst
Summary: Researchers synthesized GlcNAc mimetics and incorporated them into sLe(x) mimetics. The relationship between affinity and core conformation was analyzed using the H-1 NMR structural-reporter-group concept, and the contribution of the R-groups was quantified.
Article
Chemistry, Analytical
Marta A. Rysz, Jonny Kinzi, Anima M. Schafer, Katja In-Albon, Simone Zurcher, Seraina Schmidlin, Isabell Seibert, Oliver Schwardt, Daniel Ricklin, Henriette E. Meyer zu Schwabedissen
Summary: In this study, a bioanalytical method for simultaneous determination of atorvastatin, erlotinib, and its metabolite OSI-420 in biological samples was developed and validated. The results showed that female rats exhibited slower metabolism of erlotinib compared to male rats, and the presence of atorvastatin inhibited the metabolism of erlotinib. Non-compartmental pharmacokinetic analysis revealed a lower clearance of erlotinib when co-administered with atorvastatin.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
