Article
Biochemistry & Molecular Biology
Alessio Nocentini, Doretta Cuffaro, Lidia Ciccone, Elisabetta Orlandini, Susanna Nencetti, Elisa Nuti, Armando Rossello, Claudiu T. Supuran
Summary: A series of oxime ether-based amino alcohols were found to activate four human CA isoforms expressed in the human brain, with the most efficient activation observed for hCA II and VII. Selective hCA VII activators were identified, which could be of interest for research in therapeutic applications or as lead compounds in the search for more potent and selective CA activators.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Breeanna Mintmier, Jennifer M. McGarry, Daniel J. Bain, Partha Basu
Summary: The molybdopterin enzyme family, including the diverse dimethyl sulfoxide reductase (DMSOR) subfamily, catalyzes various reactions important in microbial processes. The molybdenum coordinating residue in these enzymes may tune substrate preference, with quantitative information and understanding still limited. Further studies on variants with different molybdenum coordinating cysteine residues provide insight into the function of these enzymes.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Johannes Karges, Ryjul W. Stokes, Seth M. Cohen
Summary: In this study, a technique for predicting the binding pose of metal-binding pharmacophores (MBPs) was proposed. By combining density functional theory (DFT) calculations and docking using a genetic algorithm, the binding of inhibitors was evaluated in silico and compared with experimental results. The computational strategy presented in this study is a useful tool for predicting metalloenzyme-MBP interactions.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Angus T. Voice, Gary Tresadern, Rebecca M. Twidale, Herman van Vlijmen, Adrian J. Mulholland
Summary: Ibrutinib is the first covalent BTK inhibitor for B-cell cancers, with uncertain mechanism previously. This study investigates multiple mechanisms of C481 modification in BTK by ibrutinib, revealing a pathway involving proton transfer and covalent bond formation. Ultimately, the findings could assist in designing covalent drugs targeting BTK and similar proteins.
Article
Chemistry, Multidisciplinary
Wenhu Zhan, Hao Zhang, John Ginn, Annie Leung, Yi J. Liu, Mayako Michino, Akinori Toita, Rei Okamoto, Tzu-Tshin Wong, Toshihiro Imaeda, Ryoma Hara, Takafumi Yukawa, Sevil Chelebieva, Patrick K. Tumwebaze, Maria Jose Lafuente-Monasterio, Maria Santos Martinez-Martinez, Jeremie Vendome, Thijs Beuming, Kenjiro Sato, Kazuyoshi Aso, Philip J. Rosenthal, Roland A. Cooper, Peter T. Meinke, Carl F. Nathan, Laura A. Kirkman, Gang Lin
Summary: Studies have shown that Plasmodium falciparum proteasome inhibitors have the potential to treat, prevent, and block transmission of malaria. A noncovalent, macrocyclic peptide inhibitor with high species selectivity and improved pharmacokinetic properties has been developed, demonstrating specific inhibition of the Pf20S beta 5 subunit.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Energy & Fuels
Sadhbhawana Dubey, Chandrakant Bhandari, Prahlad Gurjar, Sanat Kumar, Arun Kumar, Asheesh Kumar
Summary: In this study, the performance of a new chemical (crown ether) for natural gas hydrate formation kinetics and morphology was evaluated. The results showed that crown ether can significantly reduce the hydrate onset temperature and formation kinetics, and its behavior in saline water has unique characteristics.
Article
Chemistry, Multidisciplinary
Jose M. Palomo
Summary: Artificial enzymes based on protein structure modification have recently seen significant advancements, with successful synthesis using multidisciplinary strategies. However, the challenge remains in creating artificial enzymes with multiple active sites, potentially opening up new directions for enzymatic tools in sustainable chemistry. Current technologies for designing artificial enzymes with two or more active sites are limited, highlighting the need for further research in this area.
CURRENT OPINION IN GREEN AND SUSTAINABLE CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Qingqing Liu, Zhikun Liu, Wuyang Hua, Shaohua Gou
Summary: Glutathione transferase (GST P1-1) inhibitor 4n demonstrated selective inhibition towards GST P1-1 and GST M2-2, improved water solubility, and potent anticancer activities in various cancer cells, along with inducing cell cycle arrest and apoptosis in 143b cells. Pharmacokinetic studies showed favorable characteristics, and in vivo experiments on xenograft models indicated that 4n exhibited stronger antitumor effects than NBDHEX, suggesting its potential as an antitumor agent.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Meiyang Xi, Tianyu Sun, Shejie Chai, Mengjiao Xie, Siqi Chen, Liping Deng, Kui Du, Runpu Shen, Haopeng Sun
Summary: This review summarizes the relationship between phosphodiesterases and Alzheimer's disease, as well as the potential and progress of phosphodiesterase inhibitors in the treatment of this disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Dandan Zhang, Guiqing Xu, Jie Zhao, Yue Wang, Xiaofang Wu, Xing He, Wei Li, Shuting Zhang, Shouning Yang, Chunhua Ma, Yuqin Jiang, Qingjie Ding
Summary: BTK inhibitors are promising drugs for hematological tumors treatment with high selectivity and reduced side effects. Designed range of inhibitors showed potent activity in vitro and can be further developed.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Xiaoyu Qin, Kun Ye, Junxian Guo, Han Wang, Xinjian Wei, Tianfeng Chen, Hao Lin, Li Ma
Summary: Dehydrogenases are oxidoreductases that catalyze oxidative reactions in organisms to maintain redox homeostasis. Developing materials with dehydrogenase activity for the treatment of diseases with immortal proliferative properties has great potential.
SURFACES AND INTERFACES
(2023)
Article
Biochemistry & Molecular Biology
Guoyi Yan, Dongxiao Li, Xinxin Zhong, Ge Liu, Xueqin Wang, Yuanxiang Lu, Fangyuan Qin, Yuqi Guo, Shaofeng Duan, Deyu Li
Summary: In this study, virtual screening methods were used to discover two highly selective and active HDAC6 inhibitors, G1 and G10, providing insight for further development of this class of inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Multidisciplinary
Weijin Wang, Ryo Tachibana, Zhi Zou, Dongping Chen, Xiang Zhang, Kelvin Lau, Florence Pojer, Thomas R. Ward, Xile Hu
Summary: In this study, manganese transfer hydrogenases based on the biotin-streptavidin technology were designed and developed for organic synthesis. These artificial enzymes exhibit high catalytic activity and enantioselectivity, and can be utilized for a wide range of substrates and functional groups.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
William A. Denny, Jack U. Flanagan
Summary: DDR1 and DDR2 are unique discoidin domain receptor tyrosine kinases that interact with collagen in their extracellular domains before initiating signaling via tyrosine phosphorylation. Despite their sequence and structural homology with other kinases, specific DDR inhibitors have been developed, with many compounds binding to Met-704 in the DDR enzyme. While primarily used for cancer therapy, DDR inhibitors have also shown effectiveness in animal models of inflammatory conditions and kidney diseases.
Article
Biochemistry & Molecular Biology
Gloria Garcia-Galindo, Jessica Castro, Jesus Mates, Marlon Bravo, Marc Ribo, Maria Vilanova, Antoni Benito
Summary: Multi-targeted drugs may be more effective than single targeted drugs, although they may be less specific for cancer cells. In vitro experiments show that nuclear directed-ribonucleases have greater cytotoxicity for tumor cells, with the specificity mechanism not fully understood.
Article
Chemistry, Multidisciplinary
Moritz K. Jackl, Hyeonglim Seo, Johannes Karges, Mark Kalaj, Seth M. Cohen
Summary: Metalloenzyme inhibitors typically require a metal-binding pharmacophore (MBP), but MBPs can have limitations. In this study, a total of 27 salicylate metal-binding isosteres (MBIs) were synthesized as replacements for the carboxylic and hydroxyl group of the salicylic acid MBP. These salicylate MBIs were characterized for their metal-binding features, physicochemical properties, and biological activity. The results showed that salicylate MBIs can have attractive physicochemical properties and maintain or improve enzyme inhibition and selectivity.
Article
Chemistry, Organic
Johannes Karges, Seth M. Cohen
Summary: A new type of receptor molecule based on a tripodal tris(pyrrolamide) motif is presented in this study, which can bind to various anions with high affinity. The study demonstrates the ability to differentiate between enantiomeric anions through the preorganized cavity structure of the receptors.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Hyeonglim Seo, Moritz K. Jackl, Mark Kalaj, Seth M. Cohen
Summary: The use of metal-binding pharmacophores (MBPs) in drug discovery is effective for developing metalloenzyme inhibitors. 8-HQ and its derivatives are important MBPs with tunable physicochemical properties.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Johannes Karges, Ryjul W. Stokes, Seth M. Cohen
Summary: In this study, a technique for predicting the binding pose of metal-binding pharmacophores (MBPs) was proposed. By combining density functional theory (DFT) calculations and docking using a genetic algorithm, the binding of inhibitors was evaluated in silico and compared with experimental results. The computational strategy presented in this study is a useful tool for predicting metalloenzyme-MBP interactions.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Nanoscience & Nanotechnology
Dong Ju Lee, Xiaolu Yu, R. Eric Sikma, Mingqian Li, Seth M. Cohen, Zheng Chen, Guorui Cai
Summary: Metal-organic framework (MOF)-based membranes have been extensively studied as separators for lithium-sulfur (Li-S) batteries. This research investigates the property-performance relationship between MOF-based separators and Li-S batteries by adjusting the electrical conductivity, thickness, and mass loading of the MOF-based composite. The study found that the electrical conductivity of the MOF composite layer is more important than the physical/chemical trapping ability of polysulfides when the thickness is fixed. However, the trapping ability of MOFs becomes indispensable at smaller thickness, indicating the synergetic effects of the adsorption and conversion capabilities of the thin composite layer. This work highlights the importance of a holistic design consideration for MOF-based membranes in long-life and high-energy-density Li-S batteries.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Review
Chemistry, Multidisciplinary
R. Eric Sikma, Krista P. Balto, Joshua S. Figueroa, Seth M. Cohen
Summary: This Minireview discusses recent advances in low-valent MOFs and provides insights into future developments of these materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Inorganic & Nuclear
Ryan A. Dodson, Junkil Park, Jihan Kim, Matthew J. Cliffe, Seth M. Cohen
Summary: This study used oligomeric ligand precursors to prepare oligomeric-linker MOFs based on the prototypical IRMOF-1 system. It was found that IRMOF-1 was highly tolerant to oligomeric linkers and exhibited tether length-dependent ordering of ligand and metal cluster orientations. Additionally, improved low-humidity stability was observed in oligoIRMOF-1 samples.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Hyeonglim Seo, Alysia J. J. Kohlbrand, Ryjul W. W. Stokes, Jeewon Chung, Seth M. M. Cohen
Summary: Thioamides, thioureas, and thiocarbamates are introduced as stable metal-binding pharmacophores for use in metalloenzyme fragment-based drug discovery. Studies show that these molecules can act as ligands for Zn(ii)-dependent metalloenzymes including human carbonic anhydrase II and matrix metalloproteinase-2.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Conor B. O'Herin, Yuta W. Moriuchi, Troy A. Bemis, Alysia J. Kohlbrand, Michael D. Burkart, Seth M. Cohen
Summary: Human carbonic anhydrase II (hCAII) is a vital metalloenzyme in the human body, and its inhibitors have clinical applications in treating various diseases. This study developed degrader candidates targeting hCAII, which showed promising potential in inducing the degradation of hCAII. Optimization of the candidates resulted in a highly potent degrader with sustained depletion of hCAII. Mechanistic studies indicated that this optimized degrader functions similarly to previously reported CRBN-recruiting degraders.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Johannes Karges, Miriam A. Giardini, Olivier Blacque, Brendon Woodworth, Jair L. Siqueira-Neto, Seth M. Cohen
Summary: Functionalized Re(i) tricarbonyl complexes were synthesized and found to inhibit the activity of the SARS-CoV-2 main protease, presenting a potential antiviral strategy.
Letter
Chemistry, Medicinal
Ryjul W. Stokes, Alysia J. Kohlbrand, Hyeonglim Seo, Banumathi Sankaran, Johannes Karges, Seth M. Cohen
Summary: In this study, various metal-binding isosteres (MBIs) were examined to modulate the activity of the RNA-dependent RNA polymerase acidic N-terminal (PAN) endonuclease. The inhibitory ability of MBIs against PAN was evaluated using a FRET-based enzymatic assay, and their binding mode in PAN was determined using X-ray crystallography.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Samuel E. Griffin, Grant P. Domecus, Clarissa E. Flores, R. Eric Sikma, Lauren Benz, Seth M. Cohen
Summary: Low-valent metal-organic frameworks (LVMOFs) and related materials have potential applications in heterogeneous catalysis, but no catalytic activity has been observed in the reported LVMOFs. In this study, a low-valent metal-organic material constructed from phosphine linkers and Ir-I nodes is reported. This material, similar to Vaska's complex, can reversibly bind O-2 and catalyze the reductive formation of enamines from amides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Johannes Karges, Seth M. Cohen
Summary: Interest in covalent enzyme inhibitors as therapeutic agents has recently increased. In this article, the use of small, modular ReV complexes as inorganic cysteine-targeting warheads is described. These metal complexes were found to react rapidly and selectively with cysteine residues. The utility of these ReV complexes was demonstrated by their inhibition of SARS-CoV-2-associated cysteine proteases and human enzymes cathepsin B and L through the formation of adducts.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Austin Wang, Kyle Barcus, Seth M. Cohen
Summary: The surface chemistry of three MOFs, UiO-66, MIL-88B-NH2, and ZIF-8, was investigated using dye-displacement experiments. Ligand affinity on the MOF surface was found to be dependent on the metal-ligand composition. This work provides important insights for the modulation, modification, and manipulation of MOFs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Prantik Mondal, Zhaoxi Zheng, Klaus Schmidt-Rohr, Seth M. Cohen
Summary: Postsynthetic modification (PSM) is an important tool for functionalizing metal-organic frameworks (MOFs). However, the availability of organic linkers with readily modified functional groups remains a challenge. In this study, a benzene dicarboxylic acid with azidomethyl groups was synthesized and introduced into two different MOF structures. The pendant alkyl azide groups in these MOFs were amenable to PSM via click reactions. Furthermore, the pore size restriction in one of the MOFs could be overcome by using a mixed ligand approach. Importantly, the azidomethyl groups could be reduced to primary benzylic amines, maintaining the crystallinity and porosity of the MOF.
CHEMISTRY OF MATERIALS
(2023)
