Article
Immunology
Adeline Rosu, Najla El Hachem, Francesca Rapino, Kevin Rouault-Pierre, Joseph Jorssen, Joan Somja, Eve Ramery, Marc Thiry, Laurent Nguyen, Maarten Jacquemyn, Dirk Daelemans, Christopher M. Adams, Dominique Bonnet, Alain Chariot, Pierre Close, Fabrice Bureau, Christophe J. Desmet
Summary: The study reveals the crucial role of tRNA anticodon modifications in hematopoiesis, with Elp3 deficiency causing bone marrow failure and activating a p53-dependent checkpoint resembling amino acid deprivation response, ultimately promoting the development of cancer.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Plant Sciences
Mathilde Arrive, Mathieu Bruggeman, Vasileios Skaltsogiannis, Lena Coudray, Yi-Fat Quan, Cedric Schelcher, Valerie Cognat, Philippe Hammann, Johana Chicher, Philippe Wolff, Anthony Gobert, Philippe Giege
Summary: This study reveals that PRORP2 forms a complex with tRNA methyl transferases TRM1A and TRM1B in Arabidopsis, and these enzymes cooperatively participate in the maturation of cytosolic tRNAs. TRM1A/TRM1B are responsible for the m(2)(2)G26 modification of 70% cytosolic tRNAs and functionally collaborate with nuclear RNase P for early cytosolic tRNA biogenesis.
Article
Biochemistry & Molecular Biology
Brittany A. Fleming, Matthew G. Blango, Alexis A. Rousek, William M. Kincannon, Alexander Tran, Adam J. Lewis, Colin W. Russell, Qin Zhou, Lisa M. Baird, Amelia E. Barber, John R. Brannon, Connor J. Beebout, Vahe Bandarian, Maria Hadjifrangiskou, Michael T. Howard, Matthew A. Mulvey
Summary: This article investigates the impact of tRNA modifications on bacterial adaptation to environmental changes. The study reveals that bacteria can regulate the modification status of tRNA by adjusting the levels of the tRNA modifying enzyme MiaA, which in turn affects bacterial fitness and virulence. These findings uncover a rapid regulatory mechanism employed by bacteria in response to environmental shifts.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Chenchen Su, Mengqi Jin, Wenhua Zhang
Summary: The universal t(6)A modification in tRNAs plays a crucial role in stabilizing structural configurations, promoting codon-anticodon pairing, and ensuring translational accuracy. Pathogenic mutations in genes involved in t(6)A biosynthesis are linked to various mitochondrial and neurological diseases, emphasizing the importance of further research in understanding the molecular mechanisms underlying t(6)A-related disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Marie-Claire Daugeron, Sophia Missoury, Violette Da Cunha, Noureddine Lazar, Bruno Collinet, Herman van Tilbeurgh, Tamara Basta
Summary: The synthesis of t(6)A, a universal tRNA modification, is catalyzed by the KEOPS complex in Archaea and Eukaryotes. A fifth subunit, Gon7, is found only in Fungi and Metazoa. In this study, a fifth KEOPS subunit, Pcc2, is identified in Archaea and it is structurally and functionally similar to eukaryotic Gon7. Pcc2 regulates the oligomeric state of the KEOPS complex, which is conserved from Archaea to Eukaryotes.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Praneeth Bommisetti, Vahe Bandarian
Summary: This study provides critical insights into the biochemical mechanism underlying tRNA modification by the MnmEG. The formation of a flavin-iminium intermediate, FAD[N-5 & boxH;CH2](+), was identified as the central step in the MnmEG reaction, and it was demonstrated to be the universal intermediate for all MnmEG homologues. Additionally, a stable RNA-protein complex, possibly noncovalent in nature, was discovered.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Joana F. Tavares, Nick K. Davis, Ana Poim, Andreia Reis, Stefanie Kellner, Ines Sousa, Ana R. Soares, Gabriela M. R. Moura, Peter C. Dedon, Manuel Santos
Summary: The study reveals the critical role of yeast tRNA-modifying enzymes in proteostasis, with U34 modification safeguarding the proteome from translational errors, protein misfolding, and proteotoxic stress.
Article
Biochemistry & Molecular Biology
Maurice Sebastiani, Christina Behrens, Stefanie Doerr, Hans-Dieter Gerber, Rania Benazza, Oscar Hernandez-Alba, Sarah Cianferani, Gerhard Klebe, Andreas Heine, Klaus Reuter
Summary: The modified nucleoside queuosine affects translation speed and accuracy in tRNA(Asp), tRNA(Asn), tRNA(Tyr), and tRNA(His) of bacteria and eukaryotes. Eukaryotes obtain queuine as a micronutrient from food and/or the gut microbiome since they cannot synthesize queuosine de novo. The enzyme tRNA-guanine transglycosylase (TGT) catalyzes the insertion of queuine into these tRNAs, and its crystal structures and reaction mechanism have been studied to understand its medical potential, particularly in the treatment of multiple sclerosis and breast cancer.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Andreas Nguyen, Gerd Gemmecker, Charlotte A. Softley, Levon D. Movsisyan, Toni Pfaffeneder, Andreas Heine, Klaus Reuter, Francois Diederich, Michael Sattler, Gerhard Klebe
Summary: Understanding the structural arrangements of protein oligomers can support the design of ligands that interfere with their function in order to develop new therapeutic concepts for disease treatment. Recent studies have identified a novel twisted and functionally inactive form of the enzyme TGT and investigated the correlation between ligand-binding features and protein conformation. The findings suggest a potential new design concept for drug candidates.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Praneeth Bommisetti, Anthony Young, Vahe Bandarian
Summary: This article reports the in vitro biochemical reconstitution of the MnmEG reaction, demonstrating that methylene THF is the true substrate. Additionally, it is found that reduced FAD and DTT play key roles in the reaction. These findings are important for understanding the mechanism of this key tRNA modification catalyzed by MnmEG.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Chiara Tremolanti, Lorenzo Germelli, Elisabetta Barresi, Eleonora Da Pozzo, Francesca Simorini, Sabrina Castellano, Sabrina Taliani, Federico Da Settimo, Claudia Martini, Barbara Costa
Summary: Neuroinflammation is a defense mechanism in the nervous system, but improper regulation can lead to neurodegenerative diseases. TSPO, an overexpressed protein in neuroinflammation and neurodegenerative diseases, has potential in promoting neuroprotection. This review summarizes the potential effects of TSPO on neuroinflammation and related mechanisms.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Stephen Mensah, Joseph D. Rosenthal, Mamta Dagar, Tyson Brown, Jonathan J. Mills, Christopher G. Hamaker, Gregory M. Ferrence, Michael I. Webb
Summary: The evolution of high virulence bacterial strains has led to the development of novel therapeutic agents. Metal-based therapeutics, with their structural variability and unique modes of action, show great promise. This study focused on the preparation and evaluation of ruthenium(ii)-arene complexes containing Schiff base ligands with an attached ferrocene, and identified a complex with prominent activity against clinically relevant bacterial strains.
DALTON TRANSACTIONS
(2022)
Review
Pharmacology & Pharmacy
Vinay Kumar, Umesh Gupta
Summary: The combination of nanotechnology and controlled release techniques is crucial for effective drug delivery to the brain. This review article provides an in-depth and comprehensive overview of nanotechnology applications for delivering bioactive substances across the blood-brain barrier (BBB). The article focuses on tailoring the surface functionalities of nanoparticles to enhance brain delivery and discusses various targeting strategies, including receptor-mediated transcytosis. The review also explores different types of nanocarriers and their potential to improve therapeutic administration or modulate therapeutic applications in the diseased brain.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Review
Chemistry, Organic
Veda Prachayasittikul, Ratchanok Pingaew, Supaluk Prachayasittikul, Virapong Prachayasittikul
Summary: This article introduces the attractive features of 8-hydroxyquinoline (8HQ) as a potential compound for drug development and its possible therapeutic effects on Alzheimer's disease (AD). The review discusses the pathogenesis of AD and the role of metal ions in the disease, as well as the recent progress in the development of 8HQ-based neuroprotective compounds. The article concludes with a summary of the key points, providing an overview for future drug design and development in the field of neurodegenerative diseases.
Article
Chemistry, Multidisciplinary
Kumudini Paliwal, Paramita Haldar, P. K. Sudhadevi Antharjanam, Manjuri Kumar
Summary: This study characterized the isolated copper(II) complex [CuL(o-phen)]center dot H2O (1) using single-crystal X-ray crystallography. The results showed that 1 has a strong binding affinity with calf thymus DNA and human serum albumin (HSA), and exhibits potential anticancer activity by promoting DNA damage.
Article
Biochemistry & Molecular Biology
Marcela Sabou, Cecile Doderer-Lang, Caroline Leyer, Ana Konjic, Sophie Kubina, Sarah Lennon, Olivier Rohr, Stephane Viville, Sarah Cianferani, Ermanno Candolfi, Alexander W. Pfaff, Julie Brunet
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Biochemical Research Methods
Eric Chabrol, Johann Stojko, Alexandre Nicolas, Thomas Botzanowski, Benjamin Fould, Mathias Antoine, Sarah Cianferani, Gilles Ferry, Jean A. Boutin
ANALYTICAL BIOCHEMISTRY
(2020)
Article
Biochemical Research Methods
Nicolas Pythoud, Joanna Bons, Geoffroy Mijola, Alain Beck, Sarah Cianferani, Christine Carapito
Summary: Host cell proteins (HCPs) are important impurities in biopharmaceutical products, with monitoring being a critical quality attribute for monoclonal antibody (mAb) formulations. Mass spectrometry (MS) methods are emerging as powerful alternatives for HCP detection. This study developed an MS-based workflow for accurate quantification of major HCPs and measured the global HCP concentration in mAb samples. The approach proved to be reliable and sensitive, making it suitable for routine quality control in drug product analysis.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Anna Y. Belorusova, Maxime Bourguet, Steve Hessmann, Sandra Chalhoub, Bruno Kieffer, Sarah Cianferani, Natacha Rochel
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Judit Osz, Alastair G. McEwen, Maxime Bourguet, Frederic Przybilla, Carole Peluso-Iltis, Pierre Poussin-Courmontagne, Yves Mely, Sarah Cianferani, Cy M. Jeffries, Dmitri Svergun, Natacha Rochel
NUCLEIC ACIDS RESEARCH
(2020)
Article
Chemistry, Multidisciplinary
Anaelle Torres, Bastien Dalzon, Veronique Collin-Faure, Helene Diemer, Daphna Fenel, Guy Schoehn, Sarah Cianferani, Marie Carriere, Thierry Rabilloud
Article
Physics, Atomic, Molecular & Chemical
Evolene Desligniere, Marie Ley, Maxime Bourguet, Anthony Ehkirch, Thomas Botzanowski, Stephane Erb, Oscar Hernandez-Alba, Sarah Cianferani
Summary: Native mass spectrometry is extensively used to study non-covalently assembled biomolecule complexes, requiring near-neutral pH and volatile buffers to maintain proteins' native state. Online coupling of size exclusion chromatography (SEC) to nMS allows for fast automated desalting and additional separation dimension for complex protein mixtures.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2021)
Article
Multidisciplinary Sciences
Victor Lehot, Isabelle Kuhn, Marc Nothisen, Stephane Erb, Sergii Kolodych, Sarah Cianferani, Guilhem Chaubet, Alain Wagner
Summary: Research on the impact of conjugating oligonucleotides to antibodies showed that single-stranded oligonucleotides can induce consistent non-specific interactions, while double-stranded oligonucleotides have little or no effect depending on the preparation method.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Dzung Nguyen, Xiulan Xie, Stephan Jakobi, Felix Terwesten, Alexander Metz, T. X. Phong Nguyen, Vitalii A. Palchykov, Andreas Heine, Klaus Reuter, Gerhard Klebe
Summary: Interfering with protein-protein interfaces for therapeutic intervention and drug design is attractive but challenging. In this study, a cysteine-containing protein variant was used to form a disulfide linkage under oxidizing conditions, leading to a novel packing geometry of the enzyme. By breaking up the homodimeric protein using the introduced disulfide cross-link, the study demonstrated the druggability of the interface and provided essential structural and design information through transformation into a quasi-monomeric state.
ACS CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Sacnite Ramirez Rios, Anaelle Torres, Helene Diemer, Veronique Collin-Faure, Sarah Cianferani, Laurence Lafanechere, Thierry Rabilloud
Summary: The study revealed differences in mitochondrial activity and cytoskeletal structure between adherent and non-adherent cells, which may impact cellular metabolic activity and functions.
Article
Biochemistry & Molecular Biology
Maurice Sebastiani, Christina Behrens, Stefanie Doerr, Hans-Dieter Gerber, Rania Benazza, Oscar Hernandez-Alba, Sarah Cianferani, Gerhard Klebe, Andreas Heine, Klaus Reuter
Summary: The modified nucleoside queuosine affects translation speed and accuracy in tRNA(Asp), tRNA(Asn), tRNA(Tyr), and tRNA(His) of bacteria and eukaryotes. Eukaryotes obtain queuine as a micronutrient from food and/or the gut microbiome since they cannot synthesize queuosine de novo. The enzyme tRNA-guanine transglycosylase (TGT) catalyzes the insertion of queuine into these tRNAs, and its crystal structures and reaction mechanism have been studied to understand its medical potential, particularly in the treatment of multiple sclerosis and breast cancer.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Claire I. Butre, Valentina D'Atri, Helene Diemer, Olivier Colas, Elsa Wagner, Alain Beck, Sarah Cianferani, Davy Guillarme, Arnaud Delobel
Summary: The concept of multi-attribute method (MAM) has been introduced to enhance the quality-by-design process development in biopharmaceutical companies. MAM strategies rely on LC-MS technology to identify and quantify critical quality attributes (CQA) in a single assay. This study evaluated the repeatability and robustness of a benchtop LC-MS platform and bioinformatics data treatment pipelines for peptide mapping-based MAM studies, benchmarking MAM methods across laboratories using nivolumab as a case study. The results demonstrated strong interlaboratory consistency in all CQAs and emphasized the importance of bioinformatics postprocessing in MAM studies.
Article
Pharmacology & Pharmacy
Victor Lehot, Patrick Neuberg, Manon Ripoll, Francois Daubeuf, Stephane Erb, Igor Dovgan, Sylvain Ursuegui, Sarah Cianferani, Antoine Kichler, Guilhem Chaubet, Alain Wagner
Summary: Despite the success of Antibody-Drug Conjugates (ADCs), they are limited to delivering only a few cytotoxic small-molecule payloads. This study explores the potential of using cationic nanoparticles as toxic payloads, by complexing them with anti-HER2 antibody-oligonucleotide conjugates (AOC) to create Antibody-Toxic-Nanoparticles Conjugates (ATNPs). The results show selective killing of HER2-positive cells and significant tumor regression in vivo, indicating the potential of cationic nanoparticles as payloads for ADC-like strategies.
Article
Chemistry, Multidisciplinary
Bastien Dalzon, Catherine Aude-Garcia, Helene Diemer, Joanna Bons, Caroline Marie-Desvergne, Julien Perard, Muriel Dubosson, Veronique Collin-Faure, Christine Carapito, Sarah Sanglier-Cianferani, Marie Carriere, Thierry Rabilloud
ENVIRONMENTAL SCIENCE-NANO
(2020)
Article
Chemistry, Multidisciplinary
Igor Dovgan, Alexandre Hentz, Oleksandr Koniev, Anthony Ehkirch, Steve Hessmann, Sylvan Ursuegui, Sebastien Delacroix, Margaux Riomet, Frederic Taran, Sarah Cianferani, Sergii Kolodych, Alain Wagner