Article
Chemistry, Multidisciplinary
Dongqi Ni, Kang Huang, Hui Wang, Weixian Zhou, Mengyu Guo, Didar Baimanov, Yueguang Xue, Yandong Chen, Ying Liu
Summary: Antigene technology based on triplex-forming oligonucleotide (TFO) is widely used in gene-specific regulation as a potential gene therapy method. Optimizing fluorine atom (F) substitution of TFO can greatly improve the stability of triplex DNA. By combining nucleotide analogue floxuridine, a two-in-one chemo-TFO is developed, which has both gene regulation and chemotherapeutic functions.
Review
Pharmacology & Pharmacy
Yu Mikame, Asako Yamayoshi
Summary: Recent developments in artificial nucleic acid and drug delivery systems have opened up new avenues for the treatment of therapeutic oligonucleotides, offering conceptual advantages for symbiotic genome-targeting tools and complete cure of diseases. However, the potential off-target, cytotoxic, and/or immunogenic effects of nuclease-based gene-editing tools may hinder their in vivo applications.
Article
Chemistry, Analytical
Elise Daems, Debbie Dewaele, Konstantin Barylyuk, Karolien De Wael, Frank Sobott
Summary: The applications of aptamers, small oligonucleotide-based receptors with high specificity and affinity for their targets, are expanding. However, our understanding of the mechanisms governing aptamer-ligand recognition and binding is lacking, hindering the rational design of new aptamers and optimization of known ones. Using native ion mobility-mass spectrometry, the capabilities and limitations for analyzing the higher-order structure and non-covalent interactions of aptamers were demonstrated.
Article
Immunology
Naazneen Ibtehaj, Afrin Bahauddin, Maxim Ivannikov, Erik Rytting, Mohammad Jamaluddin, Yuejin Liang, Jiaren Sun, Sherry L. Haller, Xiaorong Wu, Ruksana Huda
Summary: This study compared the efficacy of unique sets of monoclonal antibody-siRNA conjugates, either individually or in combination, against different subsets of B cells in a mouse model of Myasthenia gravis. The combination treatment significantly improved the clinical symptoms and could potentially be a new therapeutic approach for MG.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Biochemistry & Molecular Biology
Shuhei Nishizawa, Gaohong Tu, Daisuke Ogata, Kouichiro Miyauchi, Akihiro Ohkubo
Summary: In this study, modified bases that can recognize T-A base pairs were developed by introducing quinoline derivatives into antiparallel TFOs. The ability of these modified bases to form triplexes and discriminate between base pairs was evaluated.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yu Mikame, Honoka Eshima, Haruki Toyama, Juki Nakao, Misaki Matsuo, Tsuyoshi Yamamoto, Yoshiyuki Hari, Jun A. Komano, Asako Yamayoshi
Summary: In this study, we investigated the photo-crosslinking properties of psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) using novel Ps-TFOs containing 2'-O,4'-C-methylene-bridged nucleic acids (Ps-LNA-mixmer). We found that the photo-crosslinking process of Ps-TFOs was not sufficient under cell irradiation conditions and highlighted the need to develop more reactive psoralen derivatives.
Article
Multidisciplinary Sciences
Siyun Chen, Tamar Getter, David Salom, Di Wu, Daniel Quetschlich, Dror S. Chorev, Krzysztof Palczewski, Carol V. Robinson
Summary: This study investigated the signalling events of G protein-coupled receptors (GPCRs) using mass spectrometry in native membranes. The findings revealed the role of native lipids in rhodopsin signalling and regeneration, and proposed a paradigm for GPCR drug discovery in native membrane environments.
Article
Chemistry, Multidisciplinary
Oliver J. Hale, Helen J. Cooper
Summary: This study demonstrates a mass spectrometry analysis method for the direct analysis of intact oligomeric membrane proteins from tissue. By characterizing protein assembly directly from sheep eye lens sections without sample pre-treatment, our approach allows for simultaneous analysis of soluble protein assemblies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Brett A. Eyford, Chaahat S. B. Singh, Thomas Abraham, Lonna Munro, Kyung Bok Choi, Tracy Hill, Rhonda Hildebrandt, Ian Welch, Timothy Z. Vitalis, Reinhard Gabathuler, Jacob A. Gordon, Hans Adomat, Emma S. T. Guns, Chieh-Ju Lu, Cheryl G. Pfeifer, Mei Mei Tian, Wilfred A. Jefferies
Summary: The study shows that the MTfp-NOX4 POC can cross the BBB, downregulate NOX4 expression, and have therapeutic effects on ischemic stroke, providing new potential treatment options for challenging neuropathologies.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemical Research Methods
Kenneth R. R. Durbin, Matthew T. T. Robey, Lilien N. N. Voong, Ryan T. T. Fellers, Corinne A. A. Lutomski, Tarick J. J. El-Baba, Carol V. V. Robinson, Neil L. L. Kelleher
Summary: Native mass spectrometry has become an important technique for determining the composition of protein complexes. However, there is a lack of software tools for comprehensive analysis of native mass spectrometry data. In this study, we introduce ProSight Native as an informatics platform that can determine the complete composition of protein complexes. We demonstrated its features by successfully determining the composition of a homotetrameric membrane complex and a heterodimer complex with associated ligands.
JOURNAL OF PROTEOME RESEARCH
(2023)
Review
Spectroscopy
Soheil Pourshahian
Summary: This article discusses the synthesis, impurities, and degradation products of oligonucleotides, as well as the application of liquid chromatography combined with mass spectrometry in the characterization and quantification of these substances. It also examines methods for determining oligonucleotide sequences through gas-phase fragmentation and indirect mass spectrometric methods.
MASS SPECTROMETRY REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Nikita Brodyagin, Ilze Kumpina, Justin Applegate, Martins Katkevics, Eriks Rozners
Summary: The research reveals that a new type of peptide nucleic acid can form stable triple helix structures with double-stranded RNA, improving the recognition of dsRNA. The study suggests insights for future development of new nucleobases to expand the sequence scope of noncoding dsRNAs that can be targeted by triplex-forming PNAs.
ACS CHEMICAL BIOLOGY
(2021)
Review
Spectroscopy
James Michael Sutton, Jaeah Kim, Noha M. El Zahar, Michael G. Bartlett
Summary: This review article provides background on the biological basis of oligonucleotides used in therapies, reviews the current state of analytical methodology, and summarizes the challenges and future perspectives for this emerging field.
MASS SPECTROMETRY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Fabien Thoreau, Lea N. C. Rochet, James R. R. Baker, Vijay Chudasama
Summary: In this article, a pyridazinedione-based trifunctional dual bridging linker was reported, which enables the generation of mAb-, Fab'-, or Fc-conjugates from native mAb, (Fab')(2), or Fc formats, respectively. The method allows for the production of various payload-antibody ratios (PARs), including heterofunctional PARs. The non-recombinant approach offers homogeneity, novelty, and accessibility to PARs, making it a suitable tool for optimizing antibody-drug conjugates and developing new antibody therapeutics.
Article
Chemistry, Analytical
Deseree J. Reid, Tapasyatanu Dash, Zhihan Wang, Craig A. Aspinwall, Michael T. Marty
Summary: Daptomycin is a cyclic lipopeptide antibiotic that interacts with lipid membranes in a non-specific manner. The interaction strength depends on membrane rigidity, with more rigid membranes showing stronger interactions. More fluid membranes may undergo pore formation to expose daptomycin to oxidation. These findings highlight the complementary use of native mass spectrometry, fast photochemical oxidation of peptides, and membrane conductance experiments in studying antibiotic-membrane interactions.
ANALYTICAL CHEMISTRY
(2023)