Article
Chemistry, Multidisciplinary
Iredia D. Iyamu, Jonah Z. Vilseck, Ravi Yadav, Nicholas Noinaj, Rong Huang
Summary: The study reports the first cell-potent NNMT bisubstrate inhibitor II399, which demonstrates strong binding affinity and selectivity for NNMT. The inhibition mechanism and crystal structure analysis reveal the interactions between II399 and both the substrate and cofactor binding pockets. This research provides a valuable probe for studying NNMT biology and introduces a strategy for developing cell-potent inhibitors for SAM-dependent methyltransferases.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Organic
Rostom Ahmed-Belkacem, Francoise Debart, Jean-Jacques Vasseur
Summary: Bisubstrate strategies address the lack of specificity in targeting methyltransferases by mimicking the transition state complex. These inhibitors have the potential to be selective therapeutics for cancers, neuropsychiatric disorders, and viral infections.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Matthias Bochtler
Summary: Most type II restriction modification systems distinguish between host and invader DNA by interrogating methylation in both DNA strands, but type IIL enzymes like DrdV are an exception to this rule. Shen et al. (2021) address how such enzymes successfully make this distinction in the latest issue of Structure.
Article
Chemistry, Medicinal
Arindam Talukdar, Ayan Mukherjee, Debomita Bhattacharya
Summary: The abnormal expression of protein methyltransferase (PMT) is related to various diseases, and the focus of current research is on the evolution from nucleoside inhibitors to selective competitive non-nucleoside inhibitors to solve the inherent problems of nucleoside analogues.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Fabio Riefolo, Rosalba Sortino, Carlo Matera, Enrique Claro, Beatrice Preda, Simone Vitiello, Sara Traserra, Marcel Jimenez, Pau Gorostiza
Summary: Tricyclic chemical structures are essential for many important drugs targeting various diseases. Researchers have developed photoisomerizable ligands based on azobenzene to mimic tricyclic structures and achieve light-controlled pharmacological action. This strategy shows effective inhibition in muscarinic acetylcholine receptors and may provide a novel approach for targeted therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Daniela P. Herrera, Andrea M. Chanique, Ascension Martinez-Marquez, Roque Bru-Martinez, Robert Kourist, Loreto P. Parra, Andreas Schuller
Summary: This study reports the engineering of a resveratrol OMT from Vitis vinifera with high catalytic efficiency in producing pterostilbene. Through point mutations and variant design, the native substrate selectivity of VvROMT was successfully altered, indicating its potential for the tailor-made production of stilbenes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Marina Baretti, Adrian. G. G. Murphy, Marianna Zahurak, Nicole Gianino, Rose Parkinson, Rosalind Walker, Tamara. Y. Y. Lopez-Vidal, Lei Zheng, Gary Rosner, Nita Ahuja, Schalper Kurt, Nilofer. S. S. Azad
Summary: This study evaluated the efficacy of PD-1 immune checkpoint inhibitor therapy in combination with DNMT and HDAC inhibitors in MMRp CRC. The results showed limited effectiveness of this combination therapy with relatively high side effects. Further research is needed to understand the epigenetic-induced immune changes and expand the potential applicability of checkpoint inhibitors in this setting.
CLINICAL EPIGENETICS
(2023)
Article
Chemistry, Multidisciplinary
Ziyin Huang, Cassandra E. Callmann, Shuya Wang, Matthew K. Vasher, Michael Evangelopoulos, Sarah Hurst Petrosko, Chad A. Mirkin
Summary: Cancer immunotherapy is a powerful treatment strategy that activates the immune system using chemistry and nanomaterials. Nanoscale materials show great potential in delivering tumor-specific antigens, adjuvants, and cytokines for effective immune response. By modulating the nanoscale structure, chemistry, and composition of immunostimulatory compounds, we can enhance immune response and reduce off-target effects. Chemistry and materials science are driving the rational design and development of next-generation cancer vaccines.
ACS CENTRAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Anthony Marchand, Lucia Bonati, Sailan Shui, Leo Scheller, Pablo Gainza, Steiphane Rosset, Sandrine Georgeon, Li Tang, Bruno E. Correia
Summary: Protein-based therapeutics, such as monoclonal antibodies and cytokines, are important treatments for various diseases, but their wide application is often limited by toxicities and adverse effects. In this study, researchers have designed and applied small-molecule-controlled switchable protein therapeutics by utilizing an OFF-switch system. By optimizing the affinity between B-cell lymphoma 2 protein and a designed protein partner, the addition of a competing drug can efficiently disrupt the protein function in vitro and lead to fast clearance in vivo. This study provides a proof-of-concept for the controllable design of protein-based therapeutics by introducing a drug-induced OFF-switch.
ACS CHEMICAL BIOLOGY
(2023)
Article
Materials Science, Biomaterials
Jie Yang, Peifen Wu, Yanlin Weng, Yayi Lin, Zhiying Chen, Fengfan Yu, Xucong Lv, Li Ni, Jinzhi Han
Summary: The emergence of multidrug-resistant bacteria poses a severe threat to global human health, and antimicrobial peptides (AMPs) have shown promise as alternatives to traditional antibiotics. In this study, a rational design strategy was used to develop seven engineered peptides with potent antimicrobial activity, among which AC7 demonstrated broad-spectrum antimicrobial activity with low cytotoxicity and hemolysis. AC7 exhibited superior abilities in disrupting cell membranes and binding to DNA, as well as effectively destroying biofilms. Furthermore, in a murine skin wound model infected with drug-resistant Pseudomonas aeruginosa, AC7 demonstrated remarkable efficacy in inhibiting wound colonization, reducing inflammatory cytokines, promoting wound healing, and enhancing immune response.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Review
Chemistry, Medicinal
Tiandi Ding, Ying Zhi, Weilin Xie, Qingqiang Yao, Bo Liu
Summary: Sphingosine kinases are lipid kinases that phosphorylate sphingosine to sphingosine-1-phosphate, playing a role in regulating biological processes; targeting their signaling pathway is a potential treatment strategy for various pathophysiological conditions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Mohsen Tatar, Masoumeh Varedi, Fakhraddin Naghibalhossaini
Summary: This study is the first to report the epigenetic effects of blackberry in cancer cells, including reduced expressions of DNMTs and HDACs, induced promoter DNA demethylation of certain genes, and increased expression of differentiation markers in colonic epithelial cells.
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
(2022)
Article
Chemistry, Medicinal
Alexander Schnitzler, Karsten Niefind
Summary: CK2, a Ser/Thr kinase, has a specific acidic substrate recognition sequence and is inhibited by polyanionic substances like heparin. This study describes the crystal structures of CK2 in complex with different heparin fragments, which provide insights into the inhibitory mechanism of heparin fragments and their chain length-dependent efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Ji Hye Kim, Byong Chul Yoo, Woo Seok Yang, Eunji Kim, Sungyoul Hong, Jae Youl Cho
Summary: Cells have developed a sophisticated signaling pathway in response to DNA damage, with protein arginine methylation playing critical roles in modulating DNA repair proteins and maintaining genome integrity. PRMTs can directly methylate DNA repair proteins or deposit methylation marks on histones to regulate various cellular processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Martina Salerno, Carmine Varricchio, Federica Bevilacqua, Dirk Jochmans, Johan Neyts, Andrea Brancale, Salvatore Ferla, Marcella Bassetto
Summary: Different viruses, such as enterovirus 71, rely on the host enzyme METTL3 to complete their cytoplasmic life cycle stages. By modulating the activity of this enzyme, it is possible to interfere with a broad range of viral infections. In this study, a series of nucleoside analogues were designed as inhibitors of human METTL3 to target multiple viral infections. Through molecular docking studies and synthesis, several novel and potent inhibitors of enterovirus 71 were identified.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Brendan G. Dwyer, Chao Wang, Daniel Abegg, Brittney Racioppo, Nan Qiu, Zhensheng Zhao, Dany Pechalrieu, Anton Shuster, Dominic G. Hoch, Alexander Adibekian
Summary: This study introduces arylazopyrazole ureas and sulfones as a new class of photoswitchable serine hydrolase inhibitors and presents a chemoproteomic platform for rapid discovery of optically controlled serine hydrolase targets in complex proteomes. The research identifies highly potent and selective photoswitchable inhibitors for drug-metabolizing enzymes, and demonstrates their pharmacological application in optically controlling drug metabolism. The study suggests the potential for using photopharmacological tools to modulate drug metabolism by controlling the activity of metabolizing enzymes, and offers synthetically accessible scaffolds for expanding to other serine hydrolases.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Mingpan Cheng, Dehui Qiu, Liezel Tamon, Eva Istvankova, Pavlina Viskova, Samir Amrane, Aurore Guedin, Jielin Chen, Laurent Lacroix, Huangxian Ju, Lukas Trantirek, Aleksandr B. Sahakyan, Jun Zhou, Jean-Louis Mergny
Summary: Recent studies have shown that i-DNA, a four-stranded cytosine-rich DNA known as the i-motif, is formed in vivo. This study tested 271 different sequences and found that i-DNA stability is nearly independent on total spacer length, with the central spacer playing a special role in stability. The study also revealed that stability depends on the length of the C-tracts at both acidic and neutral pHs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Anton Shuster, Dany Pechalrieu, Cody B. Jackson, Daniel Abegg, Hyeryun Choe, Alexander Adibekian
Summary: Arbidol (ARB) has been identified as the first clinically approved small molecule drug binder of the SARS-CoV-2 S protein, making it one of the more promising drug candidates for COVID-19.
ACS CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Organic
Mathieu Carlier, Emilie Lesur, Aurelie Baron, Aurelie Lemetais, Karine Guitot, Loic Roupnel, Christiane Dietrich, Gilles Doisneau, Dominique Urban, Nicolas Bayan, Jean-Marie Beau, Dominique Guianvarc'h, Boris Vauzeilles, Yann Bourdreux
Summary: Trehalose-based probes are useful tools for detecting the mycomembrane of mycobacteria through metabolic labeling. This study simplified the synthesis of trehalose analogues and demonstrated their application in one-step and two-step labeling methods for studying the mycomembrane in live mycobacteria.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Blaise Gatin-Fraudet, Roxane Ottenwelter, Thomas Le Saux, Stephanie Norsikian, Mathilde Pucher, Thomas Lombes, Aurelie Baron, Philippe Durand, Gilles Doisneau, Yann Bourdreux, Bogdan I. Iorga, Marie Erard, Ludovic Jullien, Dominique Guianvarc'h, Dominique Urban, Boris Vauzeilles
Summary: A novel borinic-based fluorescent probe has been developed to address the slow kinetics issue of existing designs in rapid activation by H2O2. The probe showed a reaction rate towards H2O2 10,000 times faster than its boronic counterpart, making it effective in releasing effectors like fluorescent moieties in a cellular context.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Corentin Bon, Magdalena Barbachowska, Nemanja Djokovic, Dusan Ruzic, Yang Si, Laura Soresinetti, Corinne Jallet, Ambre Tafit, Ludovic Halby, Katarina Nikolic, Paola B. Arimondo
Summary: In this study, the authors used molecular docking to design new bisubstrate inhibitors of DOT1L. They found that quinazoline can replace adenine and show similar activity with reduced cytotoxicity.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Blaise Gatin-Fraudet, Mathilde Pucher, Thomas Le Saux, Gilles Doisneau, Yann Bourdreux, Ludovic Jullien, Boris Vauzeilles, Dominique Guianvarc'h, Dominique Urban
Summary: Arylborinic acids are a new, efficient, and underexplored hydrogen peroxide-responsive triggers. This study investigated the factors that could selectively guide their oxidative rearrangement and found that the o-CF3 substituent is an excellent directing group for complete regioselectivity. This research successfully applied the findings to synthesize borinic acid-based fluorogenic probes that exclusively release the fluorescent moiety upon H2O2 treatment, maintaining their superior kinetic properties compared to boronic acids.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Multidisciplinary Sciences
Bertrand Theulot, Laurent Lacroix, Jean-Michel Arbona, Gael A. Millot, Etienne Jean, Corinne Cruaud, Jade Pellet, Florence Proux, Magali Hennion, Stefan Engelen, Arnaud Lemainque, Benjamin Audit, Olivier Hyrien, Benoit Le Tallec
Summary: Theulot et al. introduce NanoForkSpeed, a nanopore sequencing-based method to map individual replication fork velocities on entire genomes. NFS shows that fork speed is uniform across yeast chromosomes except for a marked slowdown at pausing sites.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Boris Bonaventure, Antoine Rebendenne, Ana Luiza Chaves Valadao, Mary Arnaud-Arnould, Segolene Gracias, Francisco Garcia de Gracia, Joe McKellar, Emmanuel Labaronne, Marine Tauziet, Valerie Vivet-Boudou, Eric Bernard, Laurence Briant, Nathalie Gros, Wassila Djilli, Valerie Courgnaud, Hugues Parrinello, Stephanie Rialle, Mickael Blaise, Laurent Lacroix, Marc Lavigne, Jean-Christophe Paillart, Emiliano P. Ricci, Reiner Schulz, Nolwenn Jouvenet, Olivier Moncorge, Caroline Goujon
Summary: DDX42 has been identified as an intrinsic antiviral inhibitor, restricting HIV-1 and other RNA viruses. It does not impact the replication of several negative-strand RNA viruses, suggesting a specific mode of action on target cells.
Article
Chemistry, Organic
D. Liu, O. Monfret, Y. Bourdreux, D. Urban, D. Guianvarc'h, G. Doisneau
Summary: 5-Hydroxymethyl derivatives of pyrimidine nucleosides are biologically relevant compounds. A method for the O-5 chemoselective transformation of unprotected 5-(hydroxymethyl)-2'-deoxyuridine through selective etherification in the presence of an alcohol promoted by acidic Amberlyst 15 resin at room temperature is reported. This method provides a fast, economical, and efficient access to 5-hydroxymethylated derivatives and has a broad substrate scope. It can be used to prepare useful building blocks, natural hypermodified thymidines and analogues, and cyanethyl-protected 5hmdU for solid-phase oligonucleotide syntheses.
Article
Biochemistry & Molecular Biology
Yu Luo, Anton Granzhan, Julien Marquevielle, Anne Cucchiarini, Laurent Lacroix, Samir Amrane, Daniela Verga, Jean-Louis Mergny
Summary: Besides the DNA double-helix, G-quadruplexes are non-canonical nucleic acid structures that regulate crucial biological activities. This article provides an overview of G-quadruplexes and a detailed description of the biophysical and biochemical methods used to study them in vitro. The aim is to establish guidelines for standardized research on G-quadruplexes.
Article
Multidisciplinary Sciences
Flore Nardella, Irina Dobrescu, Haitham Hassan, Fabien Rodrigues, Sabine Thiberge, Liliana Mancio-Silva, Ambre Tafit, Corinne Jallet, Veronique Cadet-Daniel, Stephane Goussin, Audrey Lorthiois, Yoann Menon, Nicolas Molinier, Dany Pechalrieu, Christophe Long, Francois Sautel, Mariette Matondo, Magalie Duchateau, Guillaume Medard, Benoit Witkowski, Artur Scherf, Ludovic Halby, Paola B. Arimondo
Summary: Malaria eradication requires the development of new drugs to combat drug-resistant parasites. Bisbenzylisoquinoline alkaloids isolated from Cocculus hirsutus were found to be active against Plasmodium falciparum blood stages. Compound 125, a derivative of these alkaloids, showed significantly improved preclinical properties and demonstrated effectiveness against drug-resistant clinical isolates and malaria transmission stages.
Article
Biochemistry & Molecular Biology
Leeroy Baron, Justine Hadjerci, Leishemba Thoidingjam, Marina Plays, Romain Bucci, Nolwenn Morris, Sebastian Muller, Fabien Sindikubwabo, Stephanie Solier, Tatiana Caneque, Ludovic Colombeau, Cedric M. Blouin, Christophe Lamaze, Alain Puisieux, Yannick Bono, Christine Gaillet, Luca Laraia, Boris Vauzeilles, Frederic Taran, Sebastien Papot, Philippe Karoyan, Romain Duval, Florence Mahuteau-Betzer, Paola Arimondo, Kevin Cariou, Gilles Guichard, Laurent Micouin, Melanie Etheve-Quelquejeu, Daniela Verga, Antoine Versini, Gilles Gasser, Cong Tang, Philippe Belmont, Andreas Linkermann, Claudia Bonfio, Dennis Gillingham, Thomas Poulsen, Marco Di Antonio, Marie Lopez, Dominique Guianvarc'h, Christophe Thomas, Geraldine Masson, Arnaud Gautier, Ludger Johannes, Raphael Rodriguez
Summary: This symposium is the third PSL Chemical Biology meeting held at Institut Curie. It originated from the Institut de Chimie des Substances Naturelles (ICSN) in Gif-sur-Yvette and expanded its scope at Institut Curie before becoming the official PSL Chemical Biology meeting. The pandemic allowed for additional speakers and the inclusion of online participants.
Article
Chemistry, Organic
Oceane Monfret, Dan Liu, Paulin Rollando, Yann Bourdreux, Dominique Urban, Gilles Doisneau, Dominique Guianvarc'h
Summary: In recent years, there has been a focus on 5-hydroxymethyl-pyrimidine-based nucleobases due to their significance in gene regulation. Several approaches have been used to synthesize properly protected 5-hydroxymethyl-pyrimidine based nucleosides, including hydroxymethylation, radical bromination, or carbonylative coupling. This study reviews these approaches, reinvestigates some of them, and proposes an alternative route based on methyl oxidation and reduction. Examples of applications, such as the synthesis of base J and 5-azidomethyl-2'-deoxyuridine, are also presented.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemical Research Methods
Alexandra Bristiel, Manon Cadinot, Mathieu Pizzonero, Frederic Taran, Dominique Urban, Raphael Guignard, Dominique Guianvarc'h
Summary: The researchers developed a facile method for conjugating relevant probes, ligands, or delivery agents onto oligonucleotides (ONs), which is important for both fundamental studies in chemical biology and improving the pharmacology of ONs in medicinal chemistry. They introduced novel 2'-functionalized nucleoside phosphoramidite monomers that contain bioorthogonal methylcyclopropene or sydnone moieties for the first time to ON solid-phase synthesis, allowing traceless ON postsynthetic modifications with reactive complementary probes through inverse electron-demand Diels-Alder reactions or strain-promoted sydnone-alkyne cycloaddition. These findings expand the bioorthogonal phosphoramidite building blocks and provide a new method for generating labeled ONs.
BIOCONJUGATE CHEMISTRY
(2023)