Article
Chemistry, Multidisciplinary
Nikita Brodyagin, Aubrey L. Maryniak, Ilze Kumpina, John M. Talbott, Martins Katkevics, Eriks Rozners, James A. MacKay
Summary: Peptide nucleic acids (PNA) with extended isoorotamides containing nucleobases (I-o) were designed to bind A-U base pairs in double-stranded RNA. Isothermal titration calorimetry and UV thermal melting experiments showed improved affinity for A-U using the Io scaffold in PNA, with PNAs having four sequential Io extended nucleobases maintaining high binding affinity.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Ryan E. Johnson, Makay T. Murray, Lucas J. Bycraft, Stacey D. Wetmore, Richard A. Manderville
Summary: A simple and efficient method for the synthesis of fluorescent molecular rotors (FMRs) is reported, which involves on-strand aldehyde capture using 6-hydroxy-indanone as a handle. The resulting internal FMR chalcones demonstrate high quantum yields, large Stokes shifts, and bright emissions in the visible region, making them suitable for various biotechnological applications.
Article
Chemistry, Organic
William J. Patterson, Kelly Lucas, Vanessa A. Jones, Zhenghua Chen, Kevin Bardelski, Melissa Guarino-Hotz, Cheyenne S. Brindle
Summary: An efficient synthesis of unsymmetrical bisindolylmethanes has been achieved by utilizing triarylmethyl cations as catalysts to facilitate the reaction between N-arylimines and two different indoles. The optimized organocatalyst allows for excellent single addition selectivity with p-nitrophenyl imines, minimizing waste and environmental impact. The reaction tolerates a broad range of imines and indole nucleophiles, producing a variety of unsymmetrical bisindolylmethanes in high yields.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Rebekah J. Karadeema, Sydney E. Morris, Luke L. Lairson, Ramanarayanan Krishnamurthy
Summary: The series of unnatural base pairs developed by the Romesberg lab have been successfully replicated, transcribed, and translated inside of a living organism. Research on the (d)NaM-(d)TPT3 UBP in 11nt duplexes showed that duplexes containing a UBP are less stable than fully natural duplexes, but generally more stable than duplexes containing natural mispairs. This work provides insights connecting the thermal stability of UBPs to replication fidelity in different sequence contexts in DNA and can assist in future UBP development.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Jinbiao Li, Shuaizhong Zhang, Jiaxin Lao, Hongbin Zou
Summary: The study introduces a non-nitro-group-assisted SNArH method for direct benzene functionalization under mild conditions, leading to the formation of luminescent compounds with subsequent structural modification for aggregation-induced emission (AIE) derivatives. This approach shows potential for specific bioprobe applications in lipid droplet localization and visualization through living cell imaging investigations.
Article
Chemistry, Analytical
Xiang Xiong, Wenya Dang, Ruxin Luo, Ying Long, Chunyi Tong, Liqin Yuan, Bin Liu
Summary: This study developed a versatile nanoprobe based on rGO and DNA probe for simultaneous visualization of miR451a and miR-214-3p in living cells, showing excellent selectivity and sensitivity. In vitro experiments demonstrated good linearity of detection signals for miR-451a and miR-214-3p, and successful dual-color imaging in human breast cancer cells was achieved using the nanoprobe.
Article
Chemistry, Multidisciplinary
Manisha B. Walunj, Seergazhi G. Srivatsan
Summary: Nucleoside-lipid conjugates are useful building blocks for constructing self-assembled architectures in biomedical and material applications. By synthetically manipulating these nucleoside derivatives, additional functionalities can be added to enhance the assembling process and impart interesting properties.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Min Gao, Sun Hyeok Lee, Sang Hyuk Park, Larissa Miasiro Ciaramicoli, Haw-Young Kwon, Heewon Cho, Joseph Jeong, Young-Tae Chang
Summary: This study presented the first fluorescent probe NeutropG for specific distinction and imaging of active neutrophils, with a selective staining mechanism elucidated as metabolism-oriented live-cell distinction (MOLD). NeutropG was successfully applied to accurately quantify neutrophil levels in fresh blood samples, showing a high correlation with the current clinical method.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Hermann Neitz, Claudia Hoebartner
Summary: We report the application of a fluorescent nucleoside called ToldU as a photoresponsive crosslinker in three different DNA architectures, resulting in enhanced fluorescence emission. The fluorogenic ToldU crosslinking reaction allows for the assembly of DNA polymers through a hybridization chain reaction, enabling the concentration-dependent detection of a specific DNA sequence. A new photoinduced fluorogenic interstrand crosslinking reaction is demonstrated in three different DNA architectures using the hydrophobic tolane-containing nucleoside, ToldU.
CHEMICAL COMMUNICATIONS
(2023)
Review
Chemistry, Analytical
Pavel G. Pronkin, Alexander S. Tatikolov
Summary: Monomethine cyanine dyes (MCDs) are widely used as biomolecular probes and stains in biochemical and biomedical research due to their ability to associate with biomolecules (mainly nucleic acids) and significantly enhance fluorescence. This review discusses the properties of MCDs, the influence of noncovalent interactions with biomacromolecules on their properties, and their use as noncovalent probes and stains for various biomacromolecules. The synthesis and photonics of MCDs, including photophysics and photochemistry, are also considered. The practical applications of MCDs in biochemistry and biomedicine are discussed.
Article
Chemistry, Multidisciplinary
Miran Lemmerer, Haoqi Zhang, Anthony J. Fernandes, Tobias Fischer, Marianne Miesskes, Yi Xiao, Nuno Maulide
Summary: Herein, we present a method for the synthesis of alpha-aryl acrylamides through polar S-to-C aryl migrations induced by a Lewis basic organocatalyst. This polar process allows subsequent elimination reactions, leading to a formal aryl/hydrogen exchange, including SO2 extrusion. The reaction is selective for electron-deficient aromatic groups and can tolerate a variety of substituents on nitrogen and in the beta-position, providing useful building blocks for further transformations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
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, Multidisciplinary
Lizhu Zhang, Cunbo Wei, Jiawen Wu, Dan Liu, Yinchao Yao, Zhuo Chen, Jianxun Liu, Chang-Jiang Yao, Dinghua Li, Rongjie Yang, Zhonghua Xia
Summary: This study demonstrates a new transition-metal and photocatalyst-free alkynylation reaction, which allows the coupling of iodoalkynes with (hetero)arenes or alkenes under visible-light irradiation. Mechanistic and computational studies reveal the process of visible light activation of iodoalkynes, and the mechanism of the reaction between the excited state iodoalkyne and C(sp(2))-H bonds to form products.
Article
Chemistry, Analytical
Dongliu Xiang, Hui Wen, Hongmei Fang, Yuan Zhou, Lei Luo, Qing Wang, Xueting Yan, Jin Huang, Jianbo Liu, Xiaohai Yang, Kemin Wang
Summary: A versatile detection technique was developed using magnetic beads, barcoded DNA strands released from gold nanoparticles, and exonuclease III cyclic cleavage-assisted signal amplification. This technique was integrated into a microfluidic chip with multiple chambers and the mixing was achieved by acoustic vibration from a portable sonic toothbrush. The detection limits of three different targets were successfully demonstrated, and this platform is expected to be developed into an automatic sample-to-answer device.
ANALYTICAL 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
Microbiology
Camila G. Quinonez, Jae Jin Lee, Juhyeon Lim, Mark Odell, Christopher P. Lawson, Amararachukwu Anyogu, Saki Raheem, Hyungjin Eoh
Summary: The fatty acid-induced dormancy-like state remodels the central carbon metabolism of Mycobacterium tuberculosis, enhancing its drug tolerance. This finding is important for understanding the adaptive strategies of M. tuberculosis and for the development of new drugs.
Article
Chemistry, Medicinal
Amalyn Nain-Perez, Anders Foller Fuchtbauer, Liliana Haversen, Aleksei Lulla, Chunxia Gao, Josipa Matic, Leticia Monjas, Alexandra Rodriguez, Paul Brear, Woonghee Kim, Marko Hyvonen, Jan Boren, Adil Mardinoglu, Mathias Uhlen, Morten Grotli
Summary: This study reports the first ADP-competitive inhibitors of liver pyruvate kinase (PKL) and identifies a specific PKL inhibitor through optimization. A structure-activity relationship study of 47 novel synthetic derivatives reveals PKL inhibitors with inhibitory activity in the nanomolar range. These results expand the understanding of the structural requirements for interactions with the ADP-binding site of PKL.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yongjin Xu, Chunxia Gao, Mans Andreasson, Liliana Haversen, Marta P. Carrasco, Cassandra Fleming, Thomas Lundback, Joakim Andreasson, Morten Grotli
Summary: In this study, photoswitchable DFG-out RET kinase inhibitors based on heterocycle-derived azobenzenes were developed, allowing for photonic control of RET activity. By modifying the molecular structure, the difference in bioactivity between the two isomers was increased. The quinoline-based compound showed the most promising results, exhibiting significant bioactivity difference in both biochemical and cellular assays.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Camila G. Quinonez, Jae Jin Lee, Juhyeon Lim, Mark Odell, Christopher P. Lawson, Amarachukwu Anyogu, Saki Raheem, Hyungjin Eoh
Summary: Unlike other bacteria, Mycobacterium tuberculosis has the ability to utilize host fatty acids as a carbon source, which contributes to its pathogenicity and drug tolerance. Identifying key enzymes involved in fatty acid metabolism is important for new drug development. Recent research has shown a link between fatty acid-induced dormancy-like state and drug tolerance via dysregulated MCC activity.
Article
Multidisciplinary Sciences
Sagar Mahale, Meenakshi Setia, Bharat Prajapati, Santhilal Subhash, Mukesh Pratap Yadav, Subazini Thankaswamy Kosalai, Ananya Deshpande, Jagannath Kuchlyan, Mirco Di Marco, Fredrik Westerlund, L. Marcus Wilhelmsson, Chandrasekhar Kanduri, Meena Kanduri
Summary: The study reveals the critical role of HnRNPK in regulating double-stranded RNA formation in loci with overlapping sense and antisense transcripts, maintaining them in a single-stranded form and determining their oncogenic functions through blocking RNA-RNA interactions.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Amalyn Nain-Perez, Oscar Nilsson, Aleksei Lulla, Liliana Haversen, Paul Brear, Sara Liljenberg, Marko Hyvonen, Jan Boren, Morten Grotli
Summary: This study describes a novel series of PKL modulators that can allosterically activate or inhibit the enzyme. These modulators were assessed for their effect on PKL activity using liver cell lysates. The study identified compounds that significantly increased PKL activity, as well as compounds that inhibited its activity. Crystal structures provided insights into the conformations of these modulators, which can be used as a reference for designing new modulators.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Nutrition & Dietetics
Umberto Maria Battisti, Chunixa Gao, Fady Akladios, Woonghee Kim, Hong Yang, Cemil Bayram, Ismail Bolat, Metin Kiliclioglu, Nursena Yuksel, Ozlem Ozdemir Tozlu, Cheng Zhang, Jihad Sebhaoui, Shazia Iqbal, Saeed Shoaie, Ahmet Hacimuftuoglu, Serkan Yildirim, Hasan Turkez, Mathias Uhlen, Jan Boren, Adil Mardinoglu, Morten Grotli
Summary: This study presents a new finding that ellagic acid and its derivatives can selectively and potently inhibit liver pyruvate kinase, which may open up new therapeutic options for non-alcoholic fatty liver disease (NAFLD).
Article
Chemistry, Medicinal
Umberto Maria Battisti, Leticia Monjas, Fady Akladios, Josipa Matic, Eric Andresen, Carolin H. Nagel, Malin Hagkvist, Liliana Haversen, Woonghee Kim, Mathias Uhlen, Jan Boren, Adil Mardinoglu, Morten Grotli
Summary: The inhibition of liver pyruvate kinase is a potential strategy for treating or reversing non-alcoholic fatty liver disease (NAFLD). Urolithin C has been identified as a promising scaffold for developing allosteric inhibitors of liver pyruvate kinase. A comprehensive structure-activity analysis of urolithin C and its analogues was conducted, revealing important chemical features for the desired activity. These findings may facilitate the discovery of more potent and selective PKL allosteric inhibitors.
Article
Cell Biology
Kathryn McIntosh, Yousif H. Khalaf, Rachel Craig, Christopher West, Ashley McCulloch, Ajay Waghmare, Christopher Lawson, Edmond Y. W. Chan, Simon Mackay, Andrew Paul, Robin Plevin
Summary: This study examined the non-canonical activation of NF kappa B signaling in U2OS cells and found that LTa1 beta(2) induced slow and sustained activation of p100 phosphorylation and increased expression of p52 NF kappa B. However, IL-1 beta and TNF alpha, canonical agonists, triggered a rapid and transient increase in pp100. This rapid phosphorylation was observed in other cell types as well, suggesting universality.
CELLULAR SIGNALLING
(2023)
Article
Chemistry, Physical
Carlos Benitez-Martin, Jean Rouillon, Morten Grotli, Joakim Andreasson
Summary: We present a tri-component photochromic molecular cocktail that can encrypt and decrypt information. The cocktail exhibits a highly non-linear fluorescent response to inputs, enabling the generation of encryption keys. The all-optical system can produce over 80 million unique fluorescence responses by applying different input combinations, and can be operated using a conventional fluorimeter.
Meeting Abstract
Biophysics
Vinoth Edal Sundar Rajan, Sune Levin, Micah J. McCauley, Mark C. Williams, Ioulia F. Rouzina, Marcus Wilhelmsson, Fredrik Westerlund
BIOPHYSICAL JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Sylvestre P. J. T. Bachollet, Nicolas Pietrancosta, Jean-Maurice Mallet, Blaise Dumat
Summary: We present a strategy that combines a protein fluorogen with the BAPTA sensing group for fluorogenic and genetic targeting of a calcium indicator. The resulting dual-input probe behaves like a fluorescent AND logic gate, with a red emission sensitive to Ca2+ that is activated only upon reaction with HaloTag, showing a 25-fold intensity enhancement. This probe can be used for wash-free calcium imaging in HeLa cells. The modular design, based on a well-established self-labeling protein tag, allows for potential tuning of photophysical properties or targeting of different analytes.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Sylvestre P. J. T. Bachollet, Yuriy Shpinov, Fanny Broch, Hela Benaissa, Arnaud Gautier, Nicolas Pietrancosta, Jean-Maurice Mallet, Blaise Dumat
Summary: This study reports the development of HaloTag fluorogens based on dipolar flexible molecular rotor structures. By modulating the electron donating and withdrawing groups, the absorption and emission wavelengths were tuned to design a palette of fluorogens with emissions spanning the green to red range, enabling multicolor imaging. Experimental and theoretical investigations were conducted, offering new insights into the design of molecular rotor-based fluorogenic HaloTag probes to improve reaction rates and imaging contrast.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Sara Liljenberg, Amalyn Nain-Perez, Oscar Nilsson, Josipa Matic, Morten Grotli
Summary: This study reports an environmentally friendly route for the synthesis of sulfonamides containing a catechol function using water as a solvent. The reaction is robust and reproducible, and eight different sulfonamides were successfully synthesized.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Microbiology
Camila G. Quinonez, Jae Jin Lee, Juhyeon Lim, Mark Odell, Christopher P. Lawson, Amararachukwu Anyogu, Saki Raheem, Hyungjin Eoh
Summary: This study reveals the metabolic changes of fatty acid-induced dormancy-like state of Mycobacterium tuberculosis and its involvement in the acquisition of drug tolerance. Mutant strains lacking MCC enzymes show different levels of drug tolerance, indicating the importance of MCC intermediates in drug tolerance mechanisms.
