Article
Chemistry, Medicinal
Hiroaki Sawamoto, Takashi Sasaki, Tomo Takegawa-Araki, Masayuki Utsugi, Hiroyuki Furukawa, Yoko Hirakawa, Fumiko Yamairi, Takashi Kurita, Karin Murahashi, Katsuya Yamada, Tetsuya Ohta, Shinji Kumagai, Akihiro Takemiya, Satoshi Obika, Jun Kotera
Summary: In this study, a novel nucleic acid, 2'-N-methanesulfonyl-2'-amino-locked nucleic acid (ALNA[Ms]), was synthesized and compared to conventional nucleic acids in terms of physical and pharmacological properties. ALNA[Ms] exhibited similar binding affinities for complementary RNA strands as conventional nucleic acids. ALNA[Ms] showed distinct biological activities from conventional constrained nucleic acids, indicating its potential as a novel modified nucleic acid in oligonucleotide therapeutics.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Yuki Kishimoto, Osamu Nakagawa, Akane Fujii, Kotaro Yoshioka, Tetsuya Nagata, Takanori Yokota, Yoshiyuki Hari, Satoshi Obika
Summary: This study presents a novel artificial nucleic acid, B-AEO, with high binding affinity, thermal stability, and resistance to nucleases, suitable for various applications.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Medicinal
Jesse Vanloon, Thad Harroun, Hongbin Yan
Summary: This study reports the first CD profiles of nucleic acids at submM concentrations, which are relevant to nucleic acid concentrations in cellular cytoplasm and nucleus, providing a new approach for studying nucleic acid conformations under biologically relevant conditions.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Tomo Takegawa-Araki, Kai Yasukawa, Norihiko Iwazaki, Masayuki Utsugi, Hiroyuki Furukawa, Shinji Kumagai, Hiroaki Sawamoto, Satoshi Obika
Summary: -Amino-LNA can acquire various functions through chemical modification at the 2 '-nitrogen atom. This study focused on the practical usefulness of 2 '-N-alkylaminocarbonyl 2 '-amino-LNA as a chemical modification of anti-miRNA oligonucleotide. The synthesis of 2 '-N-alkylaminocarbonyl substituted 2 '-amino-LNA monomers improved the duplex stability for complementary RNA strands and nuclease resistance, and increased the potency of anti-miRNA oligonucleotides.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Hector Argueta-Gonzalez, Colin S. Swenson, Kornelia J. Skowron, Jennifer M. Heemstra
Summary: This article reports experimental research using bilingual PNA sequences, which can finely tune the assembly and disassembly properties of the polymers by adjusting the properties of amino acids and the spacing of nucleic acid sequences. This has important implications for applications such as drug encapsulation and delivery.
Article
Biochemistry & Molecular Biology
Takenori Shimo, Yusuke Nakatsuji, Keisuke Tachibana, Satoshi Obika
Summary: A series of BNAs with different modifications and lengths were designed, revealing that AmNA-modified SSOs and GuNA-modified SSOs exhibited higher exon skipping activities compared to LNA-modified SSOs, but optimal design is necessary.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Gita Matuleviciute, Neringa Kleiziene, Greta Rackauskiene, Vytas Martynaitis, Aurimas Bieliauskas, Urte Sachleviciute, Rokas Jankauskas, Martynas R. Bartkus, Frank A. Slok, Algirdas Sackus
Summary: In this study, a series of new N-(aminocycloalkylene)amino acid derivatives were prepared as chiral building blocks. The method involved the conversion of enantiopure α-hydroxy acid esters into chiral triflate esters, followed by nucleophilic substitution reactions with aminopyrrolidine and aminopiperidine derivatives, resulting in the synthesis of methyl 2-[(Boc-amino)cycloamin-1-yl]alkanoates with high yield and enantio- and diastereomeric purity.
Article
Biochemistry & Molecular Biology
Tomoka Akita, Elisa Tomita-Sudo, Shin Itoh, Nae Sakimoto, Takeshi Masuda, Akifumi Nakamura, Yoshiyuki Onishi, Makoto Koizumi, Junji Kawakami
Summary: 2',4'-Bridged modifications such as LNAs and ENAs provide high binding affinity for duplex formation likely due to pre-organization. However, this study found that the introduction of 2',4'-C-bridged CRNs into DNA/RNA duplexes leads to destabilization, contrary to the previously accepted notion that 2',4'-bridged modifications always result in stabilization.
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
(2023)
Article
Food Science & Technology
Sukan Braspaiboon, Sukhuntha Osiriphun, Suthat Surawang, Wachira Jirarattanarangsri, Nattapong Kanha, Thunnop Laokuldilok
Summary: Ultrasound-assisted alkaline extraction (UAAE) was used to extract proteins from five types of algae (Arthrospira platensis, Cladophora glomerata, Porphyra tenera, Laminaria japonica and Undaria pinnatifida). The UAAE of A. platensis protein at 60% amplitude level and 30 min extraction time provided the highest protein yield and altered the surface of A. platensis. Most algal proteins were dominant in lysine and branched-chain amino acids (BCAAs). C. glomerata protein had the highest digestibility and protein digestibility-corrected amino acid scores for BCAAs. L. japonica protein was rich in aspartic and glutamic acids and had an umami taste. Algal proteins had low contents of carbohydrates and nucleic acids, while total phenolics were relatively high. They could be used as ingredients in vegan and vegetarian foods.
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
(2022)
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)
Article
Chemistry, Multidisciplinary
John M. Talbott, Brandon R. Tessier, Emily E. Harding, Grant D. Walby, Kyle J. Hess, Vladislavs Baskevics, Martins Katkevics, Eriks Rozners, James A. Mackay
Summary: Four new isoorotamide (Io)-containing PNA nucleobases have been designed for A-U recognition of double helical RNA. The experiments showed that these new PNA nucleobases have strong binding affinity, which will contribute to the future design of nucleobases capable of recognizing any sequence of double helical RNA.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
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
Biochemistry & Molecular Biology
Takahito Tomori, Koya Uekusa, Aya Koyama, Takayuki Kanagawa, Yoshiaki Masaki, Kohji Seio
Summary: A synthetic scheme was developed for the synthesis of a modified ribothymidine with a 3-(N-methylsulfamoyl)propyl group. The modification can be used to modulate the properties of oligonucleotides by changing the substituents on the nitrogen, enabling them to possess suitable properties for antisense oligonucleotides.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Ruth Aizen, Zohar A. Arnon, Or Berger, Antonella Ruggiero, Dor Zaguri, Noam Brown, Evgeny Shirshin, Inna Slutsky, Ehud Gazit
Summary: Nucleobase crystals have unique fluorescence properties in the visible spectrum, unlike their monomeric counterparts. Additionally, some nucleobases exhibit a red edge excitation shift, which is uncommon in the field of organic supramolecular materials and may have implications in therapeutic and materials science.
NANOSCALE ADVANCES
(2023)
Article
Multidisciplinary Sciences
Mohsen Mohammadniaei, Ming Zhang, Jon Ashley, Ulf Bech Christensen, Lennart Jan Friis-Hansen, Rasmus Gregersen, Jan Gorm Lisby, Thomas Lars Benfield, Finn Erland Nielsen, Jens Henning Rasmussen, Ellen Botker Pedersen, Anne Christine Rye Olinger, Laerke Torring Kolding, Maryam Naseri, Tao Zheng, Wentao Wang, Jan Gorodkin, Yi Sun
Summary: The study introduces a novel non-enzymatic isothermal amplification method for rapid detection of SARS-CoV-2 RNA, without the need for reverse transcription, with high specificity and sensitivity. The method is simple, fast, cost-effective, stable, and suitable for a wide range of testing needs.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Mathias B. Danielsen, Niels Johan Christensen, Per T. Jorgensen, Knud J. Jensen, Jesper Wengel, Chenguang Lou
Summary: Cationic moieties attached to oligonucleotides increased binding affinity and stability, with the 2'-amino-LNA analogue carrying a triaminated linker showing the most pronounced effect. Molecular modeling revealed salt-bridge formation between positively charged polyamine moieties and the dsDNA targets, resulting in the observed triplex stabilization. All investigated monomers showed increased resistance against 3'-nucleolytic digestion.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Biotechnology & Applied Microbiology
Maja van Hees, Sofie Slott, Anders Hojgaard Hansen, Heon Seok Kim, Hanlee P. Ji, Kira Astakhova
Summary: This article introduces new approaches for improving cellular uptake and endosomal escape of CRISPR-Cas9, with a focus on non-viral carriers. It also discusses the use of peptide and nanoparticle-based systems as platforms for in vivo CRISPR-Cas9 delivery.
Article
Biochemical Research Methods
Anders Dinesen, Alexander Winther, Archie Wall, Anders Maercher, Johan Palmfeldt, Vijay Chudasama, Jesper Wengel, Kurt Gothelf, James R. Baker, Kenneth A. Howard
Summary: This study aims to improve the stability of albumin-nucleic acid biomolecular drug designs by employing a fast hydrolyzing linker and nuclease resistant nucleotide analogues. The results show that the stabilized biomolecular constructs have high serum stability and retain module functionality, promoting the drug delivery potential of this biomolecular platform.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Daniela Araujo, Dalila Mil-Homens, Maria Elisa Rodrigues, Mariana Henriques, Per Trolle Jorgensen, Jesper Wengel, Sonia Silva
Summary: This study compared the efficacy of five different LNA-based antisense oligonucleotides (ASO) in controlling EFG1 gene expression and modulating filamentation and virulence of Candida albicans. The results showed that all LNA-ASOs significantly reduced filamentation and controlled EFG1 gene expression in vitro. In an in vivo model, important differences were observed in terms of reducing C. albicans virulence among the five LNA-ASOs.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Mateusz D. Tomczyk, Mariusz Zalewski, Per T. Jorgensen, Jesper Wengel, Krzysztof Walczak
Summary: The study presents novel macrocyclic polyamine-oligonucleotide conjugates and investigates their hybridization properties and thermal stability. By performing a Cu(I)-catalyzed azide-alkyne cycloaddition, macrocyclic polyamines and two DNA intercalating dyes are attached to oligonucleotides. The results show that the macrocyclic polyamine moiety has an additive and destabilizing effect on the duplex, while placing the hydrophobic dye opposite to the macrocyclic polyamine can increase the thermal stability of the duplex.
Article
Biochemistry & Molecular Biology
Jolanta Lisowiec-Wachnicka, Mathias B. Danielsen, Eugenie Abi Nader, Per T. Jorgensen, Jesper Wengel, Anna Pasternak
Summary: This study analyzed the impact of modified nucleotides on RNase H-mediated gene silencing. The results showed that introducing two LNA residues at specific positions is sufficient for efficient knock-down of the beta-actin gene. Moreover, the presence of other modified nucleotides and hairpins within the gapmers further enhanced the inhibition of beta-actin expression.
Letter
Oncology
Pilar Fajardo, Maria Taskova, Miguel A. Martin-Serrano, Jonas Hansen, Sofie Slott, Anna K. Jakobsen, Marie-Louise Wibom, Benat Salegi, Alberto Munoz, Antonio Barbachano, Arpita Sharma, John Mark Gubatan, Aida Habtezion, Juan J. Sanz-Ezquerro, Kira Astakhova, Ana Cuenda
CANCER COMMUNICATIONS
(2022)
Article
Microbiology
Andreia S. Azevedo, Ricardo M. Fernandes, Ana R. Faria, Oscar F. Silvestre, Jana B. Nieder, Chenguang Lou, Jesper Wengel, Carina Almeida, Nuno F. Azevedo
Summary: This study aimed to combine nucleic acid mimics (NAMs) and spectral image analysis to develop a new FISH variant, spectral imaging-NAM-FISH (SI-NAM-FISH), for multiplexed, robust, and rapid detection of clinical pathogens.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Joerg Duschmale, Adrian Schaeublin, Erik Funder, Steffen Schmidt, Lukasz J. Kielpinski, Helle Nymark, Klaus Jensen, Troels Koch, Martina Duschmale, Erich Koller, Marianne Ravn Moller, Simone Schadt, Christophe Husser, Andreas Brink, Sabine Sewing, Tanja Minz, Jesper Wengel, Konrad Bleicher, Meiling Li
Summary: The introduction of sulfur into chemically synthesized oligonucleotides creates stereocenters on phosphorus atoms. Only recently has it become possible to synthesize fully stereodefined antisense oligonucleotides. This article describes the application of symmetrical non-bridging PS2 linkages in the context of stereodefined locked nucleic acids (LNAs) antisense oligonucleotides, aiming to reduce chiral complexity and ultimately result in single molecules.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Osama Saher, Eman M. M. Zaghloul, Tea Umek, Daniel W. W. Hagey, Negin Mozafari, Mathias B. B. Danielsen, Alaa S. S. Gouda, Karin E. E. Lundin, Per T. T. Jorgensen, Jesper Wengel, C. I. Edvard Smith, Rula Zain
Summary: Huntington's disease is a neurodegenerative disorder caused by an abnormal increase in the length of a specific nucleotide repeat in the Huntingtin gene. A novel strategy using chemically modified oligonucleotides was found to effectively downregulate the mutant Huntingtin mRNA and protein, suggesting therapeutic potential. This study investigated the effects of different length, LNA content, and fatty acid modification of the antigene oligonucleotides on Huntingtin expression, and identified an optimized design for potential DNA-targeting therapeutics.
NUCLEIC ACID THERAPEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Weiguang Jin, Xin Li, Gael Clergeaud, Roslyn M. Ray, Marie Karen Tracy Hong Lin, Thomas Lars Andresen, Charlotte Held Gotfredsen, Martin Nielsen, Kira Astakhova, Katrine Qvortrup
Summary: This study presents a novel strategy that utilizes metalloporphyrin cages to protect and prolong the half-lives of small RNAs (sRNAs). The cage binding also facilitates the internalization of sRNAs, and the released sRNAs maintain their genetic activity in an acidic intracellular environment. Moreover, the photodynamic properties of the cage enable efficient in vitro cell killing in breast cancer treatment.
CELL REPORTS PHYSICAL SCIENCE
(2022)
Article
Chemistry, Analytical
Adriain Hernaindez Bustos, Elisa Martiny, Nadia Bom Pedersen, Rohith Pavan Parvathaneni, Jonas Hansen, Hanlee P. P. Ji, Kira Astakhova
Summary: We present an amplification-free genotyping method for determining the number of human short tandem repeats (STRs). This method, which does not require polymerase amplification, allows for accurate detection of STRs in a short timeframe and with high target DNA enrichment. The results obtained using this method are comparable to those obtained from PCR-based assays.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Maria Izabel Muniz, Adrian H. Bustos, Sofie Slott, Kira Astakhova, Gerald Weber
Summary: Monovalent and divalent cations have important roles in living cells and molecular techniques like PCR. This study examines DNA melting temperatures in magnesium and magnesium-potassium buffers using a mesoscopic model. The results are compared to previous calculations for sodium ions in terms of equivalent sodium concentration and ionic strength. The study finds that Morse potentials for hydrogen bonding are constant regardless of cation conditions, but stacking interactions are influenced by ionic strength and cation valence. The strongest variations in ionic strength occur at the sequence terminals, indicating a strong dependence of end-to-end interactions on cation valence and ionic strength.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Sofie Slott, Kira Astakhova
Summary: In this study, a new approach was described for the synthesis of microRNA pools targeting breast cancer cells. The microRNAs were synthesized simultaneously on the same solid support using the Tandem Oligonucleotide Synthesis strategy. The developed phosphoramidites allowed efficient cleavage of the microRNAs and were used to make linear and branched pools to improve product yields. This approach provides a high-yield method for synthesizing microRNA pools, which is important for nucleic acid research and technology.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Sofie Slott, Cecilie Schioth Kruger-Jensen, Izabela Ferreira da Silva, Nadia Bom Pedersen, Kira Astakhova
Summary: We present a quantitative detection method for mutated microRNA in human plasma samples. Using specific oligonucleotides designed from a Peyrard-Bishop model, we accurately predict the recognition affinity and specificity of the target and probe. Our amplification-free tandem bead-based hybridization assay achieves a limit of detection of 2.2 pM, allowing identification of single-nucleotide polymorphism mismatch profiles in microRNA-128-2-3p that correlate positively with inflammatory colitis and colorectal cancer.