Article
Chemistry, Organic
Yu-Ting Hsiao, Jonathan Beadle, Cameron Pascoe, Ritesh Annadate, John C. Vederas
Summary: The synthesis of stereochemically pure and selectively protected diamino diacids was achieved by redox decarboxylation of distal N-hydroxyphthalimide esters of protected aspartic, glutamic, or alpha-aminoadipic acids via radical addition to methylideneoxazolidinones. These products are useful for solid-supported syntheses of robust bioactive carbocyclic peptide analogs. Yields of reactive primary radical addition are superior to those of more stabilized radicals, and the reaction fails if the alkylideneoxazolidinone has a methyl substituent on its terminus (i.e., 13a/13b).
Article
Chemistry, Organic
Paula Oroz, Claudio D. Navo, Alberto Avenoza, Jesus H. Busto, Francisco Corzana, Gonzalo Jimenez-Oses, Jesus M. Peregrina
Summary: The study introduces a novel method for the chemo- and diastereoselective 1,4-conjugate additions of Se-nucleophiles to a chiral bicyclic dehydroalanine, offering a promising route for the synthesis of enantiomerically pure selenocysteine derivatives with high potential for chemical biology applications.
Article
Chemistry, Organic
Stephen G. Davies, Ai M. Fletcher, Sean M. Linsdall, Paul M. Roberts, James E. Thomson
Summary: The synthesis of various loline alkaloids was achieved through a series of reactions. The C(7) and C(7a) stereogenic centers were formed by conjugate addition and subsequent oxidation and exchange reactions. The remaining C(1) and C(2) stereogenic centers were formed through a Mannich-type reaction. The synthesis was completed by forming the 2,7-ether bridge and further manipulations.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jens Lindman, Greeshma Gopalan, Carlos Palo-Nieto, Peter Brandt, Johan Gising, Mats Larhed
Summary: In this study, a new catalytic reaction has been reported for the synthesis of a series of N-methylspiroindolines with high yield and diastereoselectivity. The stereocontrol around the spirocarbon was rationalized by density functional theory calculations and confirmed through X-ray crystallography.
Article
Energy & Fuels
Leila Keshavarz, Mohammad Reza Ghaani, Niall J. English
Summary: This study experimentally investigated the thermodynamic effects of several amines on methane hydrate formation, demonstrating their effectiveness in controlling the hydrate formation. The different amines showed varying levels of inhibition on the hydrate formation, with an overall increase in inhibition effect with concentration. The study also compared the inhibition impact of these amines with conventional thermodynamics, indicating their potential as efficient hydrate inhibitors.
Article
Chemistry, Medicinal
Xuedan Wu, Xinrui Ma, Yaofeng Zhong, Wei Chen, Muyun Xu, He Zhang, Li Wang, Xianshuang Tu, Zhaoguo Han, Weiling Zhao, Zhanhong Wu, Stergios J. Moschos, Zibo Li
Summary: Photoredox radiofluorination is a simple method to synthesize novel tryptophan-based PET agents, which have good uptake in tumor cells, making them a potential tool for precise immunotherapy monitoring.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Alina K. Bakunova, Tatiana Y. Isaikina, Vladimir O. Popov, Ekaterina Yu. Bezsudnova
Summary: D-amino acids are valuable building blocks for the synthesis of biologically active compounds and pharmaceuticals. The efficient asymmetric synthesis of optically pure D-amino acids using a pyridoxal-5'-phosphate-dependent transaminase from Haliscomenobacter hydrossis was investigated. A one-pot three-enzyme system was constructed, achieving high product yield and enantiomeric excess. Factors such as high concentration of alpha-keto acids and low reaction temperature were found to reduce cofactor leakage and increase stability of the transaminase.
Article
Chemistry, Organic
Ramana Reddy Mittapalli, Simon J. Coles, Wim T. Klooster, Adrian P. Dobbs
Summary: The aza-Prins reaction is a widely used method for synthesizing saturated nitrogen-containing heterocycles, but its lack of diastereoselectivity and formation of racemic products have been major drawbacks. In this study, the researchers successfully addressed these issues by synthesizing both diastereomerically and enantiopure multiply substituted piperidines, with potential applications in natural product synthesis.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Thorsten Kinsinger, Uli Kazmaier
Summary: The Matteson homologation with vinyl nucleophiles is an efficient and versatile protocol for the synthesis of substituted chiral allyl alcohols in a highly stereoselective fashion, which can be further transformed into highly substituted unsaturated amino acids through zinc-chelated ester-enolate Claisen rearrangements with N-protected glycine. By varying the nucleophiles used in the Matteson homologations, control over both the stereogenic centers and the side-chain substitution pattern in the newly formed gamma,delta-unsaturated amino acids can be achieved.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Gangarajulu Kesavulu, Biguvu Balachandra, Kavirayani R. Prasad
Summary: The use of lithio tris(methylthio)methane as an anion equivalent enables the synthesis of α-amino acids. Reactions with nonracemic sulfinimines yield α-sulfinamido trithioformates with excellent diastereoselectivity. Conversion of trithioformates to diverse functionalities such as α-amino acid thioesters, esters, anilides, amides, and di/tripeptides is achieved without epimerization of chiral centers.
Review
Chemistry, Applied
Hao-Qiang Cao, Jun-Kuan Li, Fa-Guang Zhang, Dominique Cahard, Jun-An Ma
Summary: This review comprehensively summarizes modern synthetic methods towards asymmetric construction of chiral amino carboxylic-phosphonic acid derivatives, including phosphono-containing amino acid derivatives and catalytic enantioselective synthesis as a potent strategy. Topics such as chiral resolution protocols, chiral auxiliary-directed syntheses, and valorization of abundant chiral amino acid resources are also discussed.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Editorial Material
Chemistry, Multidisciplinary
Bao-Le Qu, Mao-Mao Zhang, Liang-Qiu Lu, Wen-Jing Xiao
Summary: The study presents an iridium-catalyzed reaction for asymmetric synthesis of Z-allyl esters, allowing for the elegant preparation of important chiral Z-olefins.
Review
Agriculture, Dairy & Animal Science
Gabriel Cipriano Rocha, Marcos Elias Duarte, Sung Woo Kim
Summary: This study investigates the effects of reducing dietary crude protein levels while maintaining optimal ratios of amino acids on the growth performance of pigs. The results show that there is a minimum crude protein level after which the growth performance of pigs can be compromised, even with balanced essential amino acids. These findings have practical implications for formulating swine diets.
Article
Chemistry, Organic
Yu Sha, Junxue Bai, Miao Li, Wanxu Gao, Qi Yang, Jianwei Sun, Song Sun
Summary: In this study, a base-promoted sequential cyclization and carboxylation of o-alkynylamides or 2-en-4-ynamides with CO2 was achieved with high efficiency, stereoselectivity, and regioselectivity. This approach allows convenient access to diverse cyclic and fully substituted acrylates using CO2 as the carboxylic source, starting with 5-exo-dig cyclization followed by trapping the resulting vinyl anion with CO2 and MeI.
Article
Pediatrics
William S. Schleif, Robert S. Harlan, Frances Hamblin, Ernest K. Amankwah, Neil A. Goldenberg, Raquel G. Hernandez, Sara B. Johnson, Shannon Reed, David R. Graham
Summary: Newborn screening using dried plasma spots has preanalytical advantages and can effectively measure metabolites. A library of 250+ compounds was reduced to 134 through quality assurance, and 30 compounds determined the normal newborn reference ranges.
JOURNAL OF PEDIATRICS
(2022)
Article
Chemistry, Multidisciplinary
Robbert Q. Kim, Mohit Misra, Alexis Gonzalez, Ines Tomaskovic, Donghyuk Shin, Hermann Schindelin, Dmitri V. Filippov, Huib Ovaa, Ivan Dikic, Gerbrand J. Van der Heden van Noort
Summary: Legionnaires' disease is caused by Legionella pneumophila, which uses an unconventional ubiquitination process to replicate within host cells. This study synthesized analogues to investigate the mechanism and potential for new treatments. Synthetic Ub(ADPr) analogues were effective in pulling down overexpressed DupA from cell lysate.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Joanna Liwocha, David T. Krist, Gerbrand J. van der Heden van Noort, Fynn M. Hansen, Vinh H. Truong, Ozge Karayel, Nicholas Purser, Daniel Houston, Nicole Burton, Mark J. Bostock, Michael Sattler, Matthias Mann, Joseph S. Harrison, Gary Kleiger, Huib Ovaa, Brenda A. Schulman
Summary: The study reveals that the aliphatic side chain specifying reactive amine geometry is a determinant of the ubiquitin code, affecting the assembly of ubiquitin chains by replacing the acceptor site.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Guido Janssen, Susan Zhang, Remco Merkx, Christa Schiesswohl, Champak Chatterjee, K. Heran Darwin, Paul P. Geurink, Gerbrand J. van der Heden van Noort, Huib Ovaa
Summary: Tuberculosis is a global health problem caused by Mycobacterium tuberculosis infection. New drugs targeting Mtb are urgently needed due to the existence of drug resistant strains. The Pup proteasome system has been identified as a potential target for drug development, with inhibitors of Dop and PafA showing promising results in inhibiting Mtb activity.
Article
Biochemistry & Molecular Biology
Rukmini Mukherjee, Anshu Bhattacharya, Denisa Bojkova, Ahmad Reza Mehdipour, Donghyuk Shin, Khadija Shahed Khan, Hayley Hei-Yin Cheung, Kam-Bo Wong, Wai-Lung Ng, Jindrich Cinatl, Paul P. Geurink, Gerbrand J. van der Heden van Noort, Krishnaraj Rajalingam, Sandra Ciesek, Gerhard Hummer, Ivan Dikic
Summary: Famotidine has no effect on viral replication but can modulate specific signaling pathways, reducing TLR3-dependent signaling processes and subsequent activation of IRF3 and the NF-kappa B pathway, leading to control of antiviral and inflammatory responses.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Cell Biology
Yara Huppelschoten, Gerbrand J. van der Heden van Noort
Summary: Protein ubiquitination is a crucial post-translational modification that regulates cellular processes and prevents diseases. Understanding the molecular mechanisms of ubiquitination is important for deciphering this process. Chemical preparation of ubiquitin conjugates offers advantages in terms of purity and chemo-selectivity, aiding in the decoding of ubiquitin signaling.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Tom J. Harryvan, Marten Visser, Linda de Bruin, Leonie Plug, Lisa Griffioen, Arend Mulder, Peter A. van Veelen, Gerbrand J. van Der Heden van Noort, Marlieke Lm Jongsma, Miranda H. Meeuwsen, Emmanuel Jhj Wiertz, Saskia J. Santegoets, James Ch Hardwick, Thorbald Van Hall, Jacques Neefjes, Sjoerd H. Van der Burg, Lukas J. A. C. Hawinkels, Els M. E. Verdegaal
Summary: This study found that human CRC-derived CAFs have an enhanced ability to cross-present antigens, which involves the participation of lysosomal protease cathepsin S. The interaction between cross-presenting CAFs and CD8+ T cells suppresses T cell function.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Dharjath S. Hameed, Huib Ovaa, Gerbrand J. van der Heden J. van Noort, Aysegul Sapmaz
Summary: This study presents the design and development of peptides that preferentially inhibit UCH-L5 and demonstrate their ability to permeate cells and accumulate polyubiquitinated substrates, making UCH-L5 an attractive target for therapeutic purposes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yara Huppelschoten, Angela F. Elhebieshy, Dharjath S. Hameed, Aysegul Sapmaz, Jens Buchardt, Thomas E. Nielsen, Huib Ovaa, Gerbrand J. van der Heden van Noort
Summary: Chemical protein synthesis is a powerful tool to obtain uniformly modified proteins. This study successfully synthesized a 123 amino-acid nanobody against GFP using a chemical ligation-desulfurization strategy. The synthetic nanobody was functionalized with a propargyl moiety and further modified with biotin or a sulfo-cyanine5 dye. These modifications allowed for in vitro validation and microscopy imaging.
Article
Chemistry, Multidisciplinary
Jim Voorneveld, Max S. Kloet, Sven Wijngaarden, Robbert Q. . Kim, Angeliki Moutsiopoulou, Marnix Verdegaal, Mohit Misra, Ivan Dikic, Gijsbert A. . van der Marel, Herman S. Overkleeft, Dmitri V. Filippov, Gerbrand J. van der Heden van Noort
Summary: This article describes the development and optimization of a methodology for preparing peptides and proteins modified on the arginine residue with an ADPr group. The authors successfully obtained four regioisomers of ADP-ribosylated ubiquitin using this method and investigated the activity and selectivity of Legionella pneumophila ligase and hydrolase enzymes through biochemical experiments.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Yara Huppelschoten, Rishov Mukhopadhyay, Jens Buchardt, Thomas E. E. Nielsen, Alfred C. O. Vertegaal, Huib Ovaa, Gerbrand J. van Der Heden J. van Noort
Summary: Researchers synthesized a large number of SUMO-based fluorescence polarization reagents to study enzyme preferences. Screening of five SENPs revealed differences in deconjugation activity and substrate preferences. The findings provide important evidence for understanding the mechanism of SENP-specific binding to SUMO.
Article
Biochemistry & Molecular Biology
Ana G. Pedrosa, Tania Francisco, Tony A. Rodrigues, Maria J. Ferreira, Gerbrand J. van der Heden van Noort, Jorge E. Azevedo
Summary: The study investigated the extraction mechanism of PEX5 using a cell-free in vitro system and various engineered molecules. It was found that ubiquitinated PEX5 can be extracted, and the N- and C-terminus of PEX5 are not crucial for the extraction process. The study also revealed that the PEX5-linked monoubiquitin is unfolded prior to extraction, and intramolecularly cross-linked ubiquitin at residue 11 of PEX5 inhibits extraction.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Bianca D. M. van Tol, Bjorn R. van Doodewaerd, Guinevere S. M. Lageveen-Kammeijer, Bas C. Jansen, Cami M. P. Talavera Ormeno, Paul J. M. Hekking, Aysegul Sapmaz, Robbert Q. Kim, Angeliki Moutsiopoulou, David Komander, Manfred Wuhrer, Gerbrand J. van der Heden van Noort, Huib Ovaa, Paul P. Geurink
Summary: In this study, the authors develop a mass spectrometric assay to probe the activity of deubiquitinases on all diubiquitins simultaneously under substrate competition conditions, providing insights into their linkage selectivity.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yara Huppelschoten, Jens Buchardt, Thomas E. Nielsen, Aysegul Sapmaz, Gerbrand J. van der Heden van Noort
Summary: Autophagy is a cellular process that degrades materials within cells through the formation of autophagosomes. Autophagy-related proteins, including LC3A and LC3B, play a key role in autophagosome formation. The conjugation of LC3 to a phospholipid allows for the elongation of the autophagosome and facilitates the delivery of proteins for degradation. Dysregulation of autophagy has been linked to various diseases, making components of this pathway potential therapeutic targets. This study describes the synthesis of LC3 activity-based probes using native chemical ligation, which can provide insights into the mechanistic and structural details of autophagy.
Article
Biochemistry & Molecular Biology
Gabrielle B. A. van Tilburg, Andrea G. Murachelli, Alexander Fish, Gerbrand J. van der Heden van Noort, Huib Ovaa, Titia K. Sixma
Summary: This study investigates the response of the deubiquitinase UCHL3 to lysine 27-linked ubiquitin chains using synthetic ubiquitin tools, revealing that (K27)Ub(2) serves as a natural inhibitor of UCHL3. By establishing a quantitative kinetic model of the inhibitory mechanism, it is shown that (K27)Ub(2) can inhibit UCHL3 covalently and allosterically.
CELL CHEMICAL BIOLOGY
(2021)
