Article
Chemistry, Multidisciplinary
Muyun Xu, Xinrui Ma, Jessica E. Pigga, He Zhang, Shuli Wang, Weiling Zhao, Huaifu Deng, Anna M. Wu, Rihe Liu, Zhanhong Wu, Joseph M. Fox, Zibo Li
Summary: We developed a hydrophilic F-18-labeled α-TCO derivative [F-18]3 through a simple reaction. [F-18]3 can be used to construct various PET agents and imaging probes.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Umberto M. Battisti, Klas Bratteby, Jesper T. Jorgensen, Lars Hvass, Vladimir Shalgunov, Hannes Mikula, Andreas Kjaer, Matthias Manfred Herth
Summary: Combining tetrazines with F-18 labeling for pretargeted imaging shows promising results in improving imaging contrast and reducing radiation burden. Through a small-scale structure-activity relationship study, the most promising compound was selected for subsequent positron emission tomography in vivo imaging.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Wei Zheng, Xuebo Cheng, Hualong Chen, Zeng Jiang, Yuli Sun, Ziyue Yu, Tingyu Yang, Lu Zhang, Yajing Liu, Xunming Ji, Zehui Wu
Summary: The abnormal expression of aromatase is associated with various neurological diseases and tumors. In this study, F-18 and Ga-68 labeled compounds were designed and synthesized to bind to aromatase. Two of these compounds, BIBD-069 and BIBD-071, showed high affinity for aromatase. They were successfully radiolabeled and specifically bound to aromatase in vitro and in vivo. These compounds can serve as important tools for the diagnosis and treatment of aromatase-related diseases.
MOLECULAR PHARMACEUTICS
(2022)
Article
Chemistry, Medicinal
Ayoung Pyo, Misun Yun, Boreum Song, Seong-Young Kwon, Jung-Joon Min, Dong-Yeon Kim
Summary: In this study, 18F-labeled procainamide (PCA) was synthesized and evaluated for its potential as a PET imaging agent for melanoma detection. The results showed that 18F-PCA exhibited high melanoma uptake and could be a promising tool for direct melanoma detection using PET imaging.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Fabrice G. Simeon, Jae-Hoon Lee, Cheryl L. Morse, Ian Stukes, Sami S. Zoghbi, Lester S. Manly, Jeih-San Liow, Robert L. Gladding, Rachel M. Dick, Xuefeng Yan, Sabrina Taliani, Barbara Costa, Claudia Martini, Federico Da Settimo, Sabrina Castellano, Robert B. Innis, Victor W. Pike
Summary: The study aimed to develop a new TSPO imaging agent with a longer half-life and low sensitivity to human genotypes. The results showed that the 3-fluoro analog exhibited the most promising potential for PET imaging applications.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Hyeokjin Lee, Ji-Hun Park, Hyunjung Kim, Sang-keun Woo, Joon Young Choi, Kyung-Han Lee, Yearn Seong Choe
Summary: In this study, a new radioligand was developed for neuroinflammation imaging targeting CSF1R with good binding affinity and specificity. The dynamic PET/CT images showed higher uptake in the LPS-treated mouse brain. Biodistribution study demonstrated increased brain uptake in LPS mice and inhibition of uptake in LPS mice pretreated with CPPC, indicating specificity of the radioligand for CSF1R.
Article
Chemistry, Multidisciplinary
Maruthi Kumar Narayanam, Jonathan E. Tsang, Shili Xu, David A. Nathanson, Jennifer M. Murphy
Summary: Clinically tested EGFR tyrosine kinase inhibitors have been found to fail in glioblastoma patients primarily due to insufficient brain penetration, leading to inadequate exposure to the targeted cells. Molecular imaging tools can aid in the development of GBM drugs by visualizing drug distribution and confirming target expression and localization.
Article
Chemistry, Organic
Min Ho Jeon, Young-Do Kwon, Min Pyeong Kim, Gianluca Bartolini Torres, Jeong Kon Seo, Jeongmin Son, Young Hoon Ryu, Sung You Hong, Joong-Hyun Chun
Summary: The study presents a successful synthesis of various sulfamoyl [F-18]fluorides using an F-18/F-19 isotopic exchange approach, improving synthetic efficiency with radiochemical yields up to 97%. This late-stage labeling protocol offers an efficient route to diversify the chemical library possessing sulfamoyl functionalities by incorporating nucleophilic F-18 within nitrogen-containing sulfur(VI) frameworks.
Article
Biochemistry & Molecular Biology
Thu Hang Lai, Susann Schroeder, Magali Toussaint, Sladjana Dukic-Stefanovic, Mathias Kranz, Friedrich-Alexander Ludwig, Steffen Fischer, Joerg Steinbach, Winnie Deuther-Conrad, Peter Brust, Rares-Petru Moldovan
Summary: This study demonstrated the metabolic stability and specific binding of two fluorinated analogs as PET tracers in the brains of mice, with in vivo PET/MRI studies in CD-1 mice showing high initial brain uptake and rapid clearance for both radiotracers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Seo Young Kang, Yunejeong Jang, Min-Sun Cho, Soo Jeong Park, Byung Seok Moon, Hye Ok Kim, Hai-Jeon Yoon, Bom Sahn Kim
Summary: A 49-year-old man presented with sudden right-sided weakness and seizure. Imaging studies revealed a cystic mass in the left parietal lobe with features more consistent with a brain abscess than a tumor.
CLINICAL NUCLEAR MEDICINE
(2021)
Article
Chemistry, Medicinal
Rocio Garcia-Vazquez, Jesper Tranekjaer Jorgensen, Klas Erik Bratteby, Vladimir Shalgunov, Lars Hvass, Matthias M. Herth, Andreas Kjaer, Umberto Maria Battisti
Summary: Pretargeted PET imaging is a promising method for monitoring immunooncology strategies. This study successfully labeled bispyridyl tetrazines for the first time and demonstrated their application in pretargeted PET imaging. The research highlights the potential of using bispyridyl tetrazines as functionalized agents for pretargeting imaging.
Article
Medicine, Research & Experimental
Filipa Mota, Victoria R. Pell, Nisha Singh, Friedrich Baark, Edward Waters, Pragalath Sadasivam, Richard Southworth, Ran Yan
Summary: Oxidative stress plays an important role in the pathology of many human diseases. Noninvasive detection of biochemical changes in redox status is crucial for early diagnosis and prognosis. In this study, a novel F-18-labeled molecular probe, F-18-FPBT, was developed for the direct detection of superoxide using positron emission tomography (PET). The probe showed rapid and selective oxidation by superoxide in vitro and demonstrated potential clinical translation in animal models.
MOLECULAR PHARMACEUTICS
(2022)
Article
Chemistry, Multidisciplinary
Alexander P. Seiffert, Adolfo Gomez-Grande, Eva Milara, Sara Llamas-Velasco, Alberto Villarejo-Galende, Enrique J. Gomez, Patricia Sanchez-Gonzalez
Summary: Amyloid PET brain imaging is commonly used in diagnosing Alzheimer's disease, with SUVR being the most significant feature for discrimination. Texture features based on the grey-level co-occurrence matrix (HF) show potential in classifying amyloid PET images.
APPLIED SCIENCES-BASEL
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Victor L. Villemagne, Ryuichi Harada, Vincent Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Svetlana Bozinovski, Kun Huang, Brian J. Lopresti, Kazuhiko Yanai, Christopher C. Rowe, Nobuyuki Okamura
Summary: The study found that 18F-SMBT-1 is a highly selective and low nonspecific binding MAO-B tracer, which can potentially be used as a surrogate marker of reactive astrogliosis.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Hannes Leupe, Stephen Ahenkorah, Jeroen Dekervel, Marcus Unterrainer, Eric Van Cutsem, Chris Verslype, Frederik Cleeren, Christophe M. Deroose
Summary: Molecular imaging of somatostatin receptors is crucial in the clinical management of neuroendocrine tumors. PET imaging with 68Ga or 64Cu labeled somatostatin analogs is currently the gold standard, but practical and economic issues hinder widespread implementation of 68Ga imaging. Recent advancements in radiochemistry have enabled the use of 18F labeling, leading to promising clinical translations of 18F-labeled somatostatin analogs. This review presents updated clinical data and justifies the clinical application of these tracers.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Biochemical Research Methods
Anna Schwarz, Sebastian Hecko, Florian Rudroff, Jeffrey T. Kohrt, Roger M. Howard, Margit Winkler
Summary: The study introduces a novel method for aldehyde formation using carboxylic acid reductases, successfully synthesizing a pharmaceutical intermediate through a cell-free system with energy and reducing equivalents provided by auxiliary proteins.
BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Douglas Weber, David Patsch, Annika Neumann, Margit Winkler, Dorte Rother
Summary: The challenge of accessing aldehydes from carboxylate moieties was overcome by utilizing carboxylate reductases (CARs) with optimized cultivation conditions, post-translational modification, and appropriate expression strain selection to successfully increase the specific activity of Nocardia otitidiscaviarum (NoCAR) by 110-fold. This highly active NoCAR could reduce sodium benzoate to benzaldehyde with high selectivity in just 2 hours.
Article
Chemistry, Physical
Daniel Schwendenwein, Anna K. Ressmann, Marcello Entner, Viktor Savic, Margit Winkler, Florian Rudroff
Summary: This study focused on the synthesis of chiral fragrance aldehydes using a combination of chemo-catalysis and multi-enzymatic in vivo cascade reaction, as well as the development of a highly versatile high-throughput assay for enzymatic reduction of carboxylic acids. A biocompatible metal-catalyzed synthesis was used to prepare alpha or beta substituted cinnamic acid derivatives, which were then fed into a biocatalytic system for the synthesis of target molecules through enzymatic cascade reactions. The production of fragrance aldehydes was achieved by combining a biocompatible oxidative Heck protocol with specific enzymes expressed in cells.
Article
Biotechnology & Applied Microbiology
Masethabela Maria Maphatsoe, Chiam Hashem, Jonathan Guyang Ling, Melissa Horvat, Karl Rumbold, Farah Diba Abu Bakar, Margit Winkler
Summary: This study characterized a thermotolerant CAR from the white rot fungus and explored its biochemical properties and potential for immobilization, contributing to the more sustainable use of this valuable biocatalyst.
JOURNAL OF BIOTECHNOLOGY
(2022)
Article
Chemistry, Physical
Melissa Horvat, Victoria Weilch, Robert Radisch, Sebastian Hecko, Astrid Schiefer, Florian Rudroff, Birgit Wilding, Norbert Klempier, Miroslav Patek, Ludmila Martinkova, Margit Winkler
Summary: A new chemoenzymatic cascade was reported, starting with aldehyde synthesis by carboxylic acid reductase (CAR) and followed by chemical in situ oxime formation. The final step to the nitrile was catalyzed by aldoxime dehydratase (Oxd), with full conversions of phenylacetic acid and hexanoic acid achieved in a two-phase mode.
CATALYSIS SCIENCE & TECHNOLOGY
(2022)
Article
Medicine, Research & Experimental
Manu Manjunath Kanti, Isabelle Striessnig-Bina, Beatrix Irene Wieser, Silvia Schauer, Gerd Leitinger, Thomas O. Eichmann, Martina Schweiger, Margit Winkler, Elke Winter, Andrea Lana, Iris Kufferath, Leigh Matthew Marsh, Grazyna Kwapiszewska, Rudolf Zechner, Gerald Hoefler, Paul Willibald Vesely
Summary: The energy metabolism of bronchiolar club cells plays a crucial role in the repair of lung airway damage and is essential for lung health.
Article
Microbiology
Robert Radisch, Miroslav Patek, Barbora Kristkova, Margit Winkler, Vladimir Kren, Ludmila Martinkova
Summary: This review focuses on the contribution of enzymes to plant-bacteria interactions, specifically discussing substrate specificities, taxonomic and ecological distribution, and importance in selected plant symbionts. The data shows that these enzymes are abundant in Actinobacteria and Proteobacteria and play important roles in breaking through plant defenses, utilizing aldoximes or nitriles as nutrients, and potentially contributing to the synthesis of the phytohormone indole-3-acetic acid.
Review
Chemistry, Physical
Margit Winkler, Jonathan Guyang Ling
Summary: This review provides a comprehensive overview of recombinant CARs and their carboxylate substrates. It highlights the non-natural functions of CARs and summarizes the recent insights into the structure-function relationship of CARs.
Article
Chemistry, Applied
Margit Winkler, Melissa Horvat, Astrid Schiefer, Victoria Weilch, Florian Rudroff, Miroslav Patek, Ludmila Martinkova
Summary: This article introduces a cyanide-free chemoenzymatic cascade for nitrile synthesis. The reaction involves the reduction of carboxylic acid to aldehyde, followed by in situ oxime formation and finally the catalysis of oxime to nitrile. The method offers a more efficient and environmentally friendly approach to obtain various nitrile compounds.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Physical
Katharina Ebner, Lukas J. Pfeifenberger, Claudia Rinnofner, Veronika Schusterbauer, Anton Glieder, Margit Winkler
Summary: Since 2004, the study of unspecific peroxygenases (UPOs) has been conducted, which bridges the gap between P450 monooxygenases and chloroperoxidases. These enzymes are efficient biocatalysts for selective oxygenation of C-H, C=C and C-C bonds. By expressing 26 new UPOs in Komagataella phaffii, they were screened using colorimetric assays with reporter substrates such as ABTS, DMP, naphthalene, and NBD. Six UPOs from different fungi showed particularly high activity levels.
Article
Biotechnology & Applied Microbiology
Barbora Kristkova, Robert Radisch, Natalia Kulik, Melissa Horvat, Lenka Rucka, Michal Grulich, Florian Rudroff, Alan Kadek, Miroslav Patek, Margit Winkler, Ludmila Martinkova
Summary: The aim of this study was to map the sequence space of aldoxime dehydratases (Oxds) as enzymes with great potential for nitrile synthesis. In this work, a new OxdFv protein was prepared and characterized, which showed significant activity under aerobic conditions.
ENZYME AND MICROBIAL TECHNOLOGY
(2023)
Review
Chemistry, Applied
Lukas Schober, Hana Dobiasova, Valentina Jurkas, Fabio Parmeggiani, Florian Rudroff, Margit Winkler
Summary: Many aldehydes have distinct smells and are reactive functional groups used in various product synthesis. This review explores the enzymatic reactions producing aldehydes in biological systems and beyond, with some of these reactions being applicable in industrial biocatalysts.
FLAVOUR AND FRAGRANCE JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Ludmila Martinkova, Michal Grulich, Miroslav Patek, Barbora Kristkova, Margit Winkler
Summary: Lignins are complex and resistant biopolymers composed of aromatic units. The depolymerization and treatment of lignin pose challenges because of their complexity. This review focuses on biocatalyzed reactions of lignin monomers, such as vanillin, vanillic acid, syringaldehyde, and others, to produce useful chemicals. The technological maturity of these processes is evaluated, and comparisons with chemically catalyzed reactions are made.
Article
Chemistry, Multidisciplinary
Douglas Weber, Lucas de Souza Bastos, Margit Winkler, Yeke Ni, Abil E. Aliev, Helen C. Hailes, Doerte Rother
Summary: This study presents two multi-enzyme catalysed processes to produce 1,3,4-substituted tetrahydroisoquinoline (THIQ). The reduction of 3-hydroxybenzoic acid into 3-hydroxybenzaldehyde was catalysed by a carboxylate reductase enzyme. Two different recycling approaches, using purified enzymes or lyophilised whole-cells, were established and compared, with the whole-cell system showing superior performance.
Article
Chemistry, Multidisciplinary
Sebastian Arndt, Birgit Grill, Helmut Schwab, Georg Steinkellner, Urska Pogorevcnik, Dominik Weis, Alexander M. Nauth, Karl Gruber, Till Opatz, Kai Donsbach, Siegfried R. Waldvogel, Margit Winkler
Summary: This paper describes a new synthesis method for Levetiracetam using dynamic kinetic resolution and ruthenium-catalysed ex-cell anodic oxidation. High throughput screening and enzymatic resolution techniques were used to identify the necessary variants for the synthesis. The developed route provides a more sustainable access to Levetiracetam than existing ones.