Article
Biochemical Research Methods
Esau Medina, Eric J. Yik, Piet Herdewijn, John C. Chaput
Summary: XNA polymerases have great potential in synthetic biology, but little is known about their biochemical properties. This study compared various evolved polymerases and found that mutations for XNA synthesis increased substrate tolerance but could affect protein folding stability. Additionally, reverse transcriptase activity on different XNA substrates varied among polymerases. These findings can help in the development of new polymerase variants with improved activity and specificity.
ACS SYNTHETIC BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Keiji Murayama, Hiroyuki Asanuma
Summary: Xeno nucleic acids (XNAs) are analogues of DNA and RNA with non-ribose scaffolds, potentially serving as prebiotic genetic carriers or alternative genetic systems in artificial life, and as biological tools. Acyclic XNAs, lacking cyclic scaffolds, are attractive for their easy synthesis and high nuclease resistance. However, acyclic XNAs with polyanionic backbones face challenges due to high entropy cost during duplex formation.
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, Multidisciplinary
Yuuhei Yamano, Keiji Murayama, Hiroyuki Asanuma
Summary: The research demonstrates the orthogonal photo-regulation of double-strand formation between serinol nucleic acid (SNA) and RNA using different wavelengths of light and new photo-reactive nucleobases. By utilizing specific photo-switches, four hybridization states of two SNA/RNA duplexes could be orthogonally photo-controlled.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Chemistry, Multidisciplinary
Keiji Murayama, Hikari Okita, Hiroyuki Asanuma
Summary: In this article, we discuss the applications of artificial nucleic acids aTNA and SNA. The left-handed D-aTNA circuits operate correctly and are orthogonal to other nucleic acids, allowing for selective detection of right-handed D-RNA via the left-handed D-aTNA circuits. Additionally, significant progress has been made in the chemical primer extension of L-aTNA.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2023)
Review
Chemistry, Multidisciplinary
Tu Tingting, Huan Shuangyan, Ke Guoliang, Zhang Xiaobing
Summary: This review summarizes the design and applications of functional xeno nucleic acids in the biomedical field, highlighting their wide application in screening, sensing, and imaging, and addressing the limitations of natural nucleic acids.
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
(2022)
Review
Chemistry, Multidisciplinary
Tingting Tu, Shuangya Huan, Guoliang Ke, Xiaobing Zhang
Summary: Functional nucleic acids (FNAs) have been widely applied in screening, sensing, and imaging fields, but their potential application in biomedicine is limited by the drawbacks of natural nucleic acids (DNA/RNA). Xeno nucleic acids (XNAs), with chemically modified sugar groups, possess improved biological properties, making them an attractive material for biomedical applications. In this review, the design and applications of functional XNAs in the biomedical field are summarized.
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
(2022)
Article
Multidisciplinary Sciences
Helena de Puig, Rose A. Lee, Devora Najjar, Xiao Tan, Luis R. Soekensen, Nicolaas M. Angenent-Mari, Nina M. Donghia, Nicole E. Weckman, Audrey Ory, Carlos F. Ng, Peter Q. Nguyen, Angelo S. Mao, Thomas C. Ferrante, Geoffrey Lansberry, Hani Sallum, James Niemi, James J. Collins
Summary: The miSHERLOCK is a low-cost CRISPR-based POC diagnostic platform that can rapidly detect SARS-CoV-2 and its variants with high sensitivity in just 1 hour. This modular system can be quickly adapted to different viruses and variants, and is complemented by a smartphone application for output interpretation and result reporting.
Article
Biotechnology & Applied Microbiology
Peter Q. Nguyen, Luis R. Soenksen, Nina M. Donghia, Nicolaas M. Angenent-Mari, Helena de Puig, Ally Huang, Rose Lee, Shimyn Slomovic, Tommaso Galbersanini, Geoffrey Lansberry, Hani M. Sallum, Evan M. Zhao, James B. Niemi, James J. Collins
Summary: This study demonstrates the development of wearable devices functionalized with freeze-dried, cell-free synthetic circuits for noninvasive detection of biomolecules, including virus nucleic acids, without the need for living engineered bacteria. The technology shows promise for expanding opportunities in physiological status monitoring and disease detection.
NATURE BIOTECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Hui Yang, Elena Eremeeva, Mikhail Abramov, Piet Herdewijn
Summary: The study demonstrates that modified nucleic acid fragments can be transcribed into natural or modified RNA and serve as genetic templates in vivo for encoding target proteins, showcasing the potential of synthetic materials in genetics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Virology
Irani Alves Ferreira-Bravo, Jeffrey J. DeStefano
Summary: Aptamers generated using SELEX method with FANA show high affinity to RBD and S1 domains of SARS-CoV-2, directly blocking their interaction with ACE2, exhibiting high specificity and affinity similar to previous DNA aptamers.
Article
Biochemistry & Molecular Biology
Mingmei Gao, Dongying Wei, Siqi Chen, Bohe Qin, Yueyao Wang, Zhe Li, Hanyang Yu
Summary: This study reports the selection of TNAzymes with RNA endonuclease activities through in vitro selection. One of the TNAzymes, T17-22, catalyzes site-specific RNA cleavage with a k(cat) of 0.017 min(-1) and K-M of 675 nM. A fluorescent sensor based on T17-22 responds to increasing concentrations of Mg2+ with a detection limit of 0.35 mM. This TNAzyme-based sensor enables cellular imaging of Mg2+. This work provides the first proof-of-concept demonstration of using a TNA catalyst in cellular metal ion imaging.
Review
Chemistry, Medicinal
Nikolet Pavlova, Georgi Y. Miloshev, Antoniya Georgieva, Martina Traykovska, Robert Penchovsky
Summary: Synthetic biology is a emerging research field that has already found practical applications in pharmaceutical biotechnology, including metabolic engineering and drug production in genetically modified organisms. It is expected to have a significant impact on drug development and production.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Loredana Mereuta, Alina Asandei, Irina Schiopu, Jonggwan Park, Yoonkyung Park, Tudor Luchian
Summary: Nanopores offer sensitive and cost-effective single-molecule sensing capabilities, and the advent of nanopore-based DNA detection and sequencing technologies has had a significant societal impact. To address the challenge of forming stable, long-lasting single nanopores, we have developed a new approach for detecting small single-stranded DNA using dynamic hybrid constructs.
ACS APPLIED MATERIALS & INTERFACES
(2023)
News Item
Multidisciplinary Sciences
Philip Ball
Summary: A pair of studies highlight ethical and legal concerns surrounding the status of lab-grown human embryo models.
Article
Chemistry, Multidisciplinary
Hui Yang, Elena Eremeeva, Mikhail Abramov, Piet Herdewijn
Summary: The study demonstrates that modified nucleic acid fragments can be transcribed into natural or modified RNA and serve as genetic templates in vivo for encoding target proteins, showcasing the potential of synthetic materials in genetics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Abhimanyu K. Singh, Sergio E. Martinez, Weijie Gu, Hoai Nguyen, Dominique Schols, Piet Herdewijn, Steven De Jonghe, Kalyan Das
Summary: The authors discovered a transient P-pocket created by HIV reverse transcriptase while sliding over a DNA substrate and developed a cryo-EM platform for lead optimization. By screening 300 drug-like fragments, they identified two leads that bind to the P-pocket, which is resilient to drug-resistance mutations and composed of structural elements from polymerase active site, primer grip, and template-primer. An engineered RT/DNA aptamer complex was utilized to trap the transient P-pocket and structures of the RT/DNA complex in the presence of an inhibitory fragment were determined.
NATURE COMMUNICATIONS
(2021)
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
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
Biochemistry & Molecular Biology
Mohammad Hajjar, Nicholas Chim, Chao Liu, Piet Herdewijn, John C. Chaput
Summary: In this study, researchers used X-ray crystallography to investigate the recognition of pTNA nucleotides by polymerases. The findings reveal that the polymerase mediates base pairing between pTNA and DNA, providing new insights into the enzymatic synthesis of XNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Leah Goulding, Eleonora Kiss, Robert Vrancken, Nesya Goris, Min Luo, Elisabetta Groaz, Piet Herdewijn, Linda Dixon
Summary: African swine fever virus is a highly contagious hemorrhagic viral disease that causes significant losses in the domestic pig population. Since there are currently no vaccines available, finding effective antiviral agents is crucial. This study identified two compounds that can effectively inhibit the replication of African swine fever virus, showing potential as prophylactic and therapeutic agents.
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
Lauriane Rietmeyer, Ines Li de la Sierra-Gallay, Guy Schepers, Delphine Dorchene, Laura Iannazzo, Delphine Patin, Thierry Touze, Herman van Tilbeurgh, Piet Herdewijn, Melanie Etheve-Quelquejeu, Matthieu Fonvielle
Summary: Xenobiotic nucleic acids (XNAs) have great potential in synthetic biology, biotechnology, and molecular medicine. However, their ability to mimic nucleic acids needs further exploration. In this study, we synthesized three L-Ala-tXNAs analogs to investigate their ability to mimic tRNA. We found that L-Ala-tXNAs containing HNA or 2' F-RNA could be substrates of a bacterial Fem transferase. The synthesis of peptidyl-XNA and its binding with the enzyme demonstrated the impact of XNA on protein binding. This is the first report of functional tXNA in an in vitro assay, suggesting the potential of using tXNA as a substitute for tRNA in translation.
NUCLEIC ACIDS RESEARCH
(2022)
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
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)
