Article
Chemistry, Organic
Matthieu Roignant, Jun Zhang, Julien Brioche, Serge R. Piettre
Summary: This study describes a new approach to protected modified dinucleotides using a difluorophosphinothioyl unit to replace the phosphoryl diester. The authors report a simple and high-yielding method for the preparation of 6'-iodonucleosides and successfully synthesize bisfuranosyl derivatives featuring both a difluorophosphinothioyl unit and a nucleobase. However, the introduction of the second nucleobase resulted in low yields and the formation of mixtures of homo- and heterodinucleotides due to the trans-N-glycosylation process.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Daniela Perrone, Elena Marchesi, Lorenzo Preti, Maria Luisa Navacchia
Summary: The click chemistry approach is widely used for bioconjugations in medicinal chemistry, allowing the design of new hybrid compounds with diverse applications. Nucleoside analogs play a significant role in cancer therapy and virus treatment, and new targeted oligonucleotides have been developed for various purposes in pharmacological applications. This review outlines the latest research on the use of click chemistry methodology in the field of nucleosides, nucleotides, and nucleic acids.
Article
Chemistry, Multidisciplinary
Pallavi Rungta, Manish Kumar, Priyanka Mangla, Sandeep Kumar, Ashok K. Prasad
Summary: The study introduced spirocyclic restriction into nucleosides to achieve structural pre-organisation, leading to the synthesis of C-4 '-hydroxyl-tetrahydrofurano-spironucleosides. Assessing the selectivity of monoacylation in the sugar derivative revealed that different acyl chain lengths could increase reaction rate without affecting enzyme selectivity. The modification of a hydroxytetrahydrofuran ring in furano-nucleosides demonstrated the ability to generate C4'-exo, NE-conformational restriction in nucleosides.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Biochemical Research Methods
Ines C. Santos, Michael Lanzillotti, Ignat Shilov, Maria Basanta-Sanchez, Abhishek Roushan, Rose Lawler, Wilfred Tang, Marshall Bern, Jennifer S. Brodbelt
Summary: With the development of RNA-based therapeutics, the need for analytical methods to confirm sequences and map modifications has become urgent. This study compares different mass spectrometry techniques for sequencing modified nucleic acids and finds that UV photodissociation and activated electron photodetachment dissociation are effective for characterizing modified nucleic acids. However, different modifications can affect the fragmentation pathways and sequence coverage.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Chemistry, Organic
Alexander Pontarelli, Christopher J. Wilds
Summary: This study describes the synthesis of C5-propynyl-2'-fluoroarabinonucleic acids (FANAP) and reveals that these modifications enhance RNA binding and support RNase H mediated cleavage. These findings suggest that C5-propynyl ANA/FANA modifications have promising potential for the design of therapeutic ONs.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Alexander Pontarelli, Christopher J. Wilds
Summary: The clinical success of the antisense approach for the treatment of genetic disorders is due to the chemical modifications of the oligonucleotide scaffold. C5-propynyl modified nucleobases of fluoroarabinonucleic acids demonstrate enhanced RNA binding and support RNase H mediated cleavage, expanding the range of antisense competent modifications.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Dagmara Baraniak, Jerzy Boryski
Summary: This review discusses the use of triazole-modified nucleic acids in various fields, highlighting the valuable properties of the 1,2,3-triazole unit obtained through click chemistry. It explores the biological activities of this modification, as well as its potential applications in therapeutic settings and synthetic genes.
Article
Chemistry, Physical
Yunxiao Zhang, Yizhi Zhang, Youyuan Guo, Shanshan Liu, Xiao Shen
Summary: This research demonstrates a visible-light-induced photo-catalyst strategy for preparing both gem-difluoroalkenes and trifluoromethyl alkanes from alpha-CF3-olefins. The selectivity of the reactions depends on the choice of catalyst rather than the modification of substrate structures.
Article
Chemistry, Multidisciplinary
John F. Gallagher, Niall Hehir, Pavle Mocilac, Chloe Violin, Brendan F. O'Connor, Emmanuel Aubert, Enrique Espinosa, Benoit Guillot, Christian Jelsch
Summary: A 3 x 3 isomer grid of nine N-(chlorophenyl)pyridinecarboxamides (NxxCl) was reported, and their physicochemical studies and single crystal structures were investigated. The research revealed that some of the NxxCl crystal structures share similar features with their halogenated and methylated counterparts. Additionally, the favored hydrogen bonding mode in the NxxCl series is the aggregation by N-H center dot center dot center dot N-pyridine interactions, and amide center dot center dot center dot amide intermolecular interactions were observed in certain compounds.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Biochemistry & Molecular Biology
Sunil Nath
Summary: This study introduces a new theory of oxygen exchange and applies it to ATP hydrolysis by the mitochondrial F-1-ATPase. The results suggest that steady-state ATP hydrolysis by F-1-ATPase occurs with all three sites occupied by Mg-nucleotide, contradicting previous bisite models and supporting the trisite catalysis formulated by Nath's torsional mechanism.
Article
Chemistry, Medicinal
Wanlei Wei, Candide Champion, Zhaomin Liu, Stephen J. Barigye, Paul Labute, Nicolas Moitessier
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Chemistry, Medicinal
Jessica Plescia, Stephane De Cesco, Mihai Burai Patrascu, Jerry Kurian, Justin Di Trani, Caroline Dufresne, Alexander S. Wahba, Naela Janmamode, Anthony K. Mittermaier, Nicolas Moitessier
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Jessica Plescia, Caroline Dufresne, Naela Janmamode, Alexander S. Wahba, Anthony K. Mittermaier, Nicolas Moitessier
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Wanlei Wei, Candide Champion, Stephen J. Barigye, Zhaomin Liu, Paul Labute, Nicolas Moitessier
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2020)
Article
Chemistry, Physical
Mihai Burai Patrascu, Joshua Pottel, Sharon Pinus, Michelle Bezanson, Per-Ola Norrby, Nicolas Moitessier
Article
Biochemistry & Molecular Biology
Kevin A. Uggowitzer, Yeganeh Habibi, Wanlei Wei, Nicolas Moitessier, Christopher J. Thibodeaux
Summary: Class II lanthipeptide synthetases catalyze the modification of precursor peptides into lanthipeptides with high control. Studies on HalM2 enzyme show that dynamic structural elements are essential for its proper function.
Review
Chemistry, Medicinal
Julie Ross, Caitlin E. Miron, Jessica Plescia, Patricia Laplante, Kevin McBride, Nicolas Moitessier, Tarik Moroy
Summary: The MYC oncogene is a high priority target for clinical intervention in cancer patients, with direct small molecule inhibition traditionally facing challenges due to its intrinsically disordered nature. However, recent strategies for indirectly targeting MYC, such as MYC guanine quadruplex stabilization and disruption of MYC:MAX heterodimer, have emerged with the advancement of protein structural information and computational tools in medicinal chemistry.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Anne Labarre, Julia K. Stille, Mihai Burai Patrascu, Andrew Martins, Joshua Pottel, Nicolas Moitessier
Summary: Structure-based design programs, particularly docking small molecules to proteins, have become important in drug discovery. However, many of these tools are primarily developed for enzyme inhibitors, relying heavily on hydrogen bonds and electrostatic and hydrophobic interactions. This article describes new features implemented into FITTED to broaden its applicability to covalent enzyme inhibitors and metalloenzymes. The updated program was tested for its ability to predict the correct binding mode of drug-sized molecules in various proteins.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Krikor Bijian, Dominik Wernic, Anita K. Nivedha, Jie Su, Felicia Phei Lin Lim, Caitlin E. Miron, Hind Amzil, Nicolas Moitessier, Moulay A. Alaoui-Jamali
Summary: Compound 2e is a potent small molecule that selectively inhibits Aurora A kinase and multiple PKC isoforms. It showed significant inhibition of colony forming ability and metastasis development in breast cancer cells. The critical role of selenium-containing side chains within 2e was revealed to improve its selectivity and potency by forming additional interactions and modulating protein dynamics.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Itai Sharon, Sharon Pinus, Marcel Grogg, Nicolas Moitessier, Donald Hilvert, T. Martin Schmeing
Summary: Cyanophycin synthetase CphA1 is capable of synthesizing cyanophycin without exogenous primers, utilizing a cryptic metallopeptidase-like active site in its N-terminal domain to digest cyanophycin into primers. Primer dependence of CphA1 in heterologous hosts may be a limiting factor for cyanophycin production.
NATURE COMMUNICATIONS
(2022)
Review
Chemistry, Multidisciplinary
Guanyu Wang, Nicolas Moitessier, Anthony K. Mittermaier
Summary: This article discusses the development of covalent drugs over the past century and recent advancements in covalent drug research, with a focus on computational and biophysical methods in the design of prolyl oligopeptidase (POP) and SARS-CoV-2 3CL(pro) covalent inhibitors.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Benjamin Weiser, Jerome Genzling, Mihai Burai-Patrascu, Ophelie Rostaing, Nicolas Moitessier
Summary: This study investigates the ML-augmented docking method, which combines machine learning techniques with molecular docking, for predicting CYP inhibition. The results demonstrate that ML-augmented docking significantly improves the accuracy of docking software and shows better generalizability.
Review
Chemistry, Organic
Mihai Burai Patrascu, Jessica Plescia, Amit Kalgutkar, Vincent Mascitti, Nicolas Moitessier