Article
Chemistry, Multidisciplinary
Pulak Ghosh, Heike M. Kropp, Karin Betz, Samra Ludmann, Kay Diederichs, Andreas Marx, Seergazhi G. Srivatsan
Summary: This study demonstrates the use of environment-sensitive heterocycle-modified fluorescent nucleotide substrates to probe the incorporation mechanism of DNA polymerases in real-time and at the atomic level. The results show that different nucleotide analogs have varying incorporation efficiencies in different DNA polymerase families, and some modified nucleotides can serve as reporters for monitoring enzyme activity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Simon Pospisil, Alessandro Panattoni, Filip Gracias, Veronika Sykorova, Viola Vankova Hausnerva, Dragana Vitovska, Hana Sanderova, Libor Krasny, Michal Hocek
Summary: By systematically studying five 2'-deoxyribonucleotide triphosphates (dNTPs) derived from epigenetic pyrimidines, it was found that these modified pyrimidine dNTPs can be incorporated into DNA by DNA polymerases. This incorporation of modified nucleotides into DNA could potentially lead to gene silencing and affect the replication of modified bacteriophage genomes.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Ayesha Naseer, Faisal Abdulrhman Osra, Asia Naz Awan, Aqeel Imran, Abdul Hameed, Syed Adnan Ali Shah, Jamshed Iqbal, Zainul Amiruddin Zakaria
Summary: The rapid development of resistance by ureolytic bacteria, such as those associated with gastric and duodenal cancer, has created a need for a new therapy with anti-urease activity. A series of pyridine carboxamide and carbothioamide derivatives were synthesized and investigated for their inhibitory action against urease. Two derivatives, 5-chloropyridine-2-yl-methylene hydrazine carbothioamide (Rx-6) and pyridine 2-yl-methylene hydrazine carboxamide (Rx-7), exhibited significant activity. Molecular docking and kinetic studies were conducted to understand the binding mode and interaction of the most potent inhibitors with urease. ADME profile showed that all synthesized molecules had oral bioavailability and high GI absorption.
Article
Chemistry, Multidisciplinary
Xin Xiao, San Hua Lim, Wei Chu, Yan Liu
Summary: Tailoring the metal properties over N-doped carbon materials is crucial for lignocellulose/cellobiose hydrogenation reactions. By adjusting the metal-support interaction and optimizing the content of N, excellent catalytic performance was achieved, indicating N-doped carbon materials as promising supports for a wide range of biomass hydrogenation.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2021)
Article
Agronomy
Dongyan Yang, Xin Qi, Tatiana A. Kalinina, Tatiana Glukhareva, Liangfu Tang, Zhengming Li, Zhijin Fan
Summary: The plant elicitor candidate 3g was found to potentially act on the salicylic acid signaling pathway, as evidenced by up-regulation of genes related to reactive oxygen species, pathogenesis-related protein, and salicylic acid signaling. N-(2-phenyl-3-pyridyl) thiadiazole/isothiazole carboxamide analogs may serve as promising lead scaffolds for further investigation as novel plant elicitors.
PEST MANAGEMENT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Yilan Zhao, Honghao Yang, Fengshou Wu, Xiaogang Luo, Qi Sun, Weiliang Feng, Xiulian Ju, Genyan Liu
Summary: A series of potential fructose-1,6-bisphosphatase (FBPase) inhibitors for type II diabetes mellitus treatment were identified through computational modeling. The study provided important insights into the development of novel FBPase inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Eunsun Park, Sun Joo Lee, Heegyum Moon, Jongmi Park, Hyeonho Jeon, Ji Sun Hwang, Hayoung Hwang, Ki Bum Hong, Seung-Hee Han, Sun Choi, Soosung Kang
Summary: JAK1 inhibition presents a promising therapeutic strategy for various diseases by designing selective inhibitors. In particular, the compound 31g showed potent activity against JAK1 and inhibited TGF-beta-induced HSCs migration effectively.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mohamed H. Hekal, Paula S. Farag, Magdy M. Hemdan, Wael M. El-Sayed
Summary: This study synthesized a series of N-(1,3,4-thiadiazol-2yl)furan-2-carboxamide derivatives and found higher yields and rates under microwave conditions compared to traditional methods. The antiproliferative activities of these compounds were assessed, showing promising results against three cancer cell lines and VEGFR-2 as a potential molecular target. Some compounds exhibited significant antiproliferative activity, with Compound 7 identified as the best inhibitor of VEGFR-2.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Claire Dutson, Esther Allen, Mark J. Thompson, Joseph H. Hedley, Heather E. Murton, David M. Williams
Summary: This study synthesized C5-modified dUTP and dCTP nucleotides labeled with a dianionic reporter group, and investigated the effects of linker length and mode of attachment to the nucleobase on substrate properties with various DNA polymerases. The results showed that nucleotides containing a PEG linker attached to the nucleobase via an amide bond were the best substrates, and nucleotides with PEG linkers ranging from PEG(6) to PEG(24) could be incorporated by several DNA polymerases.
Article
Chemistry, Physical
Efrain Polo-Cuadrado, Karoll Ferrer, Edison Osorio, Ivan Brito, Jonathan Cisterna, Margarita Gutierrez
Summary: The organo-crystalline compound N-(4-acetylphenyl)quinoline-3-carboxamide (4) was successfully synthesized and its structure was characterized using various spectroscopic methods and single crystal X-ray diffraction. Geometrical optimizations and theoretical UV-Vis spectrum analysis were carried out, showing good agreement with experimental results.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Chemistry, Applied
Yen Hoang Pham, Viktor A. Trush, Maria Korabik, Volodymyr M. Amirkhanov, Paula Gawryszewska
Summary: The study describes the structural, optical, and magnetic properties of lanthanide coordination compounds with N-(diphenylphosphoryl)pyrazine-2-carboxamide as an antenna, which showed excellent performance in converting UV radiation into near-infrared light. The compounds exhibit behavior of field-induced Single Ion Magnets (SIMs) with high effective energy barrier values, demonstrating potential applications in molecular magnets with optimized infrared emission.
Article
Chemistry, Medicinal
Fei Liu, Bin Wang, Yanlong Liu, Wei Shi, Zhongyuan Hu, Xiayun Chang, Xujing Tang, Ying Zhang, Hongjiang Xu, Ying He
Summary: In this study, we reported the design, synthesis, and structure-activity relationships (SARs) of N-(methyl-d3) pyridazine-3carboxamide derivatives as TYK2 inhibitors. Compound 24 exhibited acceptable inhibition activity against STAT3 phosphorylation and demonstrated satisfactory selectivities toward other members of JAK family. Moreover, compound 24 showed good stability profile in liver microsomal assay and reasonable pharmacokinetics (PK) exposures. In anti-CD40-induced colitis models, compound 24 was orally highly effective with no significant hERG and CYP isozymes inhibition. These findings highlight the potential of compound 24 as a candidate for the development of anti-autoimmunity diseases agents.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Applied
Athanasios Markos, Lukas Janecky, Tomas Chvojka, Tomas Martinek, Hector Martinez-Seara, Blanka Klepetarova, Petr Beier
Summary: This study presents a novel aluminum halide-mediated synthesis of N-haloalkenyl imidoyl halides, which is highly versatile and provides highly functionalized products. The reaction mechanism involves the opening of the triazole ring, N-2 elimination, and halide exchange reactions.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Engineering, Chemical
Jinxiang Liu, Yujie Yan, Yiwei Feng, Shengli Liu
Summary: This study uses first principle calculation method to investigate the molecular mechanisms of poly(N-alkyl methacrylamides) as KHIs and reveals the impact of alkyl pendant groups on their inhibition performance.
CHEMICAL ENGINEERING SCIENCE
(2022)
Article
Chemistry, Medicinal
Yue Qiao, Yang Zhang, Zhenrui Qiao, Wenya He, Yingda Chen, Depu Song, Guohao Wang, Ning Guo, Lulian Shao, Zhiyong Tian, Qiang Wang, Lin Yan, Hai Qian
Summary: In this study, novel molecules based on the key pharmacophore structures of classic TRPV1 ligands were designed and synthesized, and a potent TRPV1 antagonist with excellent central nervous system penetration and bioavailability was identified. The findings provide a valuable lead for the development of novel TRPV1 antagonists.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Eric Largy, Alexander Konig, Anirban Ghosh, Debasmita Ghosh, Sanae Benabou, Frederic Rosu, Valerie Gabelica
Summary: Nucleic acids have been important targets for cancer drugs and antibiotics, and mass spectrometry offers unique advantages for studying their noncovalent structures.
Article
Biochemistry & Molecular Biology
Hoai Nguyen, Mikhail Abramov, Jef Rozenski, Elena Eremeeva, Piet Herdewijn
Summary: Chemically modified nucleic acids are of great interest in synthetic biology for creating a regulatable and sophisticated synthetic system. Researchers have successfully synthesized modified DNA sequences and introduced them into eukaryotic cells, which is important for scientists working in the field of xenobiology in yeast.
Article
Chemistry, Medicinal
Shuai Tan, Elisabetta Groaz, Raj Kalkeri, Roger Ptak, Brent E. Korba, Piet Herdewijn
Summary: Minor structural modifications of acyclic nucleoside phosphonates can significantly affect their antiviral properties. This study reveals a shift in the selectivity spectrum of acyclic nucleoside phosphonates towards hepatitis B virus (HBV) by 2-substitution of their acyclic chain. The modified nucleotides exhibited significant anti-HBV activities, with the (S)-enantiomers demonstrating higher potency than the (R)-forms. A phosphonodiamidate prodrug of (S)-EHPMPG showed promising anti-HBV activity with high selectivity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Abhimanyu K. Singh, Brent De Wijngaert, Marc Bijnens, Kris Uyttersprot, Hoai Nguyen, Sergio E. Martinez, Dominique Schols, Piet Herdewijn, Christophe Pannecouque, Eddy Arnold, Kalyan Das
Summary: A protocol for rapid structure determination of HIV-1 reverse transcriptase (RT) complexes by cryo-electron microscopy (cryo-EM) has been optimized. Six structures of RT complexes with nonnucleoside inhibitors were determined, revealing important differences in structure and conformation. These differences have implications for understanding drug resistance mechanisms and drug design.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemical Research Methods
Eric Largy, Bruno Alies, Guillaume Condesse, Alexandra Gaubert, Thomas Livingston, Karen Gaudin
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Niklas Freund, Alexander Taylor, Sebastian Arangundy-Franklin, Nithya Subramanian, Sew-Yeu Peak-Chew, Amy M. Whitaker, Bret D. Freudenthal, Mikhail Abramov, Piet Herdewijn, Philipp Holliger
Summary: In this study, a two-residue "gate" was discovered in an archaeal DNA polymerase, which enables the synthesis of 2'-modified RNA oligomers. This discovery expands the application potential of 2'-modified RNA in nucleic acid therapeutics and biotechnology.
Article
Chemistry, Multidisciplinary
Nina Khristenko, Frederic Rosu, Eric Largy, Jerome Haustant, Cedric Mesmin, Valerie Gabelica
Summary: Native ion mobility mass spectrometry has potential applications in the biophysical characterization of proteins, as the charge state distribution and collision cross section distribution depend on the solution conformation. This study investigates the charging and gas-phase conformation of multi-domain therapeutic proteins with globular domains tethered by disordered linkers. The results suggest a hybrid ionization mechanism, where globular domains are ejected one at a time from a parent droplet.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Shenghua Gao, Letian Song, Hongtao Xu, Antonios Fikatas, Merel Oeyen, Steven De Jonghe, Fabao Zhao, Lanlan Jing, Dirk Jochmans, Laura Vangeel, Yusen Cheng, Dongwei Kang, Johan Neyts, Piet Herdewijn, Dominique Schols, Peng Zhan, Xinyong Liu
Summary: DF-47 and DF-51 were identified as effective inhibitors of SARS-CoV-2/DENV polymerase through RdRp inhibition screening and in vitro antiviral study. In silico simulation revealed stable binding modes between DF-47/DF-51 and SARS-CoV-2/DENV RdRp, including chelating with Mg2+ near the polymerase active site. These polyphenols have the potential to be developed into broad-spectrum, non-nucleoside RdRp inhibitors with a new scaffold.
Article
Biochemistry & Molecular Biology
Hui Yang, Elena Eremeeva, Mikhail Abramov, Maarten Jacquemyn, Elisabetta Groaz, Dirk Daelemans, Piet Herdewijn
Summary: An enzymatic method was developed to generate partially base-modified RNA constructs, as well as fully modified RNA constructs featuring multiple modified bases. The efficiency of the fully modified RNA constructs was enhanced by using different T7 RNA polymerase variants. The study also demonstrated the successful incorporation of modified bases into PCR products and the effectiveness of the modified RNA constructs in CRISPR-Cas9 cleavage assays.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Microbiology
Jean Guillon, Anita Cohen, Clotilde Boudot, Sarah Monic, Solene Savrimoutou, Stephane Moreau, Sandra Albenque-Rubio, Camille Lafon-Schmaltz, Alexandra Dassonville-Klimpt, Jean-Louis Mergny, Luisa Ronga, Mikel Bernabeu de Maria, Jeremy Lamarche, Cristina Dal Lago, Eric Largy, Valerie Gabelica, Serge Moukha, Pascale Dozolme, Patrice Agnamey, Nadine Azas, Catherine Mullie, Bertrand Courtioux, Pascal Sonnet
Summary: A series of novel 2,9-bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives were designed, synthesized, and evaluated for their anti-protozoan activity. The results showed promising activity against Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei, with low cytotoxicity against human HepG2 cells.
Article
Chemistry, Analytical
Eric Largy, Matthieu Ranz
Summary: Hydrogen-deuterium exchange mass spectrometry (HDX/MS) is used for studying protein conformation dynamics and characterizing oligonucleotide conformations and their interactions with cations, small molecules, and proteins. OligoR is a web-based application that provides dedicated solutions for processing and visualizing native HDX/MS data of oligonucleotides. It offers a simple and robust approach to deconvoluting bimodal isotope distributions and can be extended to various analytes. The results are presented in interactive data tables and can be exported as publication-quality figures.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Cecile Gasse, Puneet Srivastava, Guy Schepers, Joachim Jose, Marcel Hollenstein, Philippe Marliere, Piet Herdewijn
Summary: Chemical cell surface modification is an important field with great potential in tissue engineering, cell-based immunotherapy, and regenerative medicine. However, research on engineering bacterial tissues through chemical cell surface modification is lacking, especially in finding suitable molecular handles. In this study, a novel strategy using orthogonal nucleic acid-protein conjugation was developed to induce artificial bacterial aggregation. This system combines the selective and stable linkage of a protein Tag at the cell surface with the modularity and reversibility of aggregation through oligonucleotide hybridization. The immobilization of XNA via covalent, SNAP-tag-mediated interactions on cell surfaces for bacterial aggregation is reported for the first time.
Article
Biochemistry & Molecular Biology
Pradeep S. Pallan, Terry P. Lybrand, Eriks Rozners, Mikhail Abramov, Guy Schepers, Elena Eremeeva, Piet Herdewijn, Martin Egli
Summary: Efforts are being made to create and implement alternative genetic systems with pairing components orthogonal to natural base pairs. Another approach conserves Watson-Crick pairing but substitutes one or all of the four letters of the DNA alphabet with modified components. This study analyzes the properties of a DZA DDD structure and reveals interesting findings regarding stability, hydration, structure, and dynamics.
Article
Biochemistry & Molecular Biology
Peter Schofield, Alexander Taylor, Jerome Rihon, Cristian D. Pena Martinez, Sacha Zinn, Charles-Alexandre Mattelaer, Jennifer Jackson, Gurpreet Dhaliwal, Guy Schepers, Piet Herdewijn, Eveline Lescrinier, Daniel Christ, Philipp Holliger
Summary: Nucleic acids serve as the basis of heredity and are increasingly utilized to create novel nanostructures, devices, and drugs. Chemically modified alternatives, known as xeno nucleic acids (XNAs), have been developed to expand their chemical and functional capabilities. XNA aptamers, which can bind targets with high affinity and specificity, have not been thoroughly investigated in terms of their structure and function.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mengmeng Wang, Kunyu Qu, Peipei Zhao, Xin Yin, Yiwei Meng, Piet Herdewijn, Chao Liu, Lixin Zhang, Xuekui Xia
Summary: Gemcitabine prodrugs with modifications on the 4-N-amino group by employing an acetylated L- or D-lysine moiety masked by different substitutions were synthesized. These prodrugs showed higher anticancer activity than gemcitabine in A549 lung cells and exhibited potent activity against BxPC-3 pancreatic cells. They also showed lower toxicity towards normal cells and improved stability in various metabolic environments. Overall, acetylated lysine conjugated gemcitabine prodrugs could be promising leads for new anticancer drugs.
RSC MEDICINAL CHEMISTRY
(2023)
