Article
Biochemistry & Molecular Biology
Yu-Chen Yen, Annalissa M. Kammeyer, Jagannadharao Tirlangi, Arun K. Ghosh, Andrew D. Mesecar
Summary: This study developed a platform to produce large amounts of pure BACE2 protein and designed compounds that selectively inhibit BACE1 over BACE2. The research findings could lead to the quicker development of new selective BACE inhibitors for treating Alzheimer's disease or type II diabetes.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Eyoas Ergetu Areda, Jose Rodrigo Cordova-Alarcon, Hirokazu Masui, Mengu Cho
Summary: This article introduces an innovative design concept for nanosatellites, particularly suitable for mass production missions that require high efficiency and fast delivery. By using a flexible modular structural platform and a new mounting method, productivity can be maximized and the satellite integration process can be simplified and made more efficient.
APPLIED SCIENCES-BASEL
(2022)
Review
Chemistry, Multidisciplinary
Thomas M. Privalsky, Alexander M. Soohoo, Jinhua Wang, Christopher T. Walsh, Gerard D. Wright, Eric M. Gordon, Nathanael S. Gray, Chaitan Khosla
Summary: The increasing prevalence of multidrug-resistant bacteria has become an urgent health crisis, requiring renewed investment in the discovery and development of antibiotics. A multifaceted approach is necessary to address the antibacterial resistance crisis, with a focus on exploring validated antibacterial targets and lead molecules. Creative techniques, such as studying underexplored ecological niches or utilizing available data from genome mining efforts, can help in the search for new antibiotic leads.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Jingyan Fan, Zhiming Yao, Chaoyue Yan, Meilin Hao, Jun Dai, Wenjin Zou, Minghui Ni, Tingting Li, Lu Li, Shuo Li, Jie Liu, Qi Huang, Rui Zhou
Summary: Macrolides, including tylosin, are widely used antibiotics. This study focuses on improving tylosin yield by enhancing the catalytic activity of the key enzyme TylF in its biosynthesis process in Streptomyces fradiae.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Chemistry, Physical
Fangyi Li, Jizhou Jiang, Jiamei Wang, Jing Zou, Wei Sun, Haitao Wang, Kun Xiang, Pingxiu Wu, Jyh-Ping Hsu
Summary: Carbon-based materials have attracted great interest for their unique properties and breakthroughs in clean energy applications. However, their low selectivity and poor conductivity have hindered their commercialization. To improve hydrogen production efficiency, researchers are exploring ways to increase surface area, create interconnected porous channels, and enhance stability of carbon-based materials. This review summarizes the structural advantages and performance improvements of various porous carbon-based materials and evaluates the performance of hydrogen production methods. The role of active sites in promoting charge transport, electrical conductivity, and stability during hydrogen production is discussed. Challenges and future directions for the development of high-efficiency hydrogen 3D porous carbon-based materials are also discussed.
Article
Chemistry, Medicinal
Arash Sadri
Summary: Target-based drug discovery, although dominant, lacks a comprehensive evaluation of its efficiency, as demonstrated by a manual review of 32000 articles and patents spanning 150 years. Only 9.4% of small-molecule drugs have been discovered through target-based assays, and their therapeutic effects cannot be solely attributed to their intended targets due to off-target mechanisms. This suggests that a reductionist approach may be the cause of the current productivity crisis, and an evidence-based approach using tools like artificial intelligence and machine learning may enhance efficiency.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shunsuke Kato, Koki Takeuchi, Motonao Iwaki, Kentaro Miyazaki, Kohsuke Honda, Takashi Hayashi
Summary: Affinity purification of recombinant proteins is an essential technique in biotechnology. However, current methods are costly, limiting their versatile use. To address this issue, we developed the CSAP system, using commercially available chitin powder as a chromatography matrix for low-cost purification of Strep-tag II fusion proteins. We demonstrated the system's effectiveness in protein screening using 96-well format, identifying potential candidates for an abiotic carbene transfer reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Liang Xiong, Xin Mao, Yinping Guo, Yangli Zhou, Mingxin Chen, Pei Chen, Shengyong Yang, Linli Li
Summary: The study identified Cpd8 and Cpd10 as highly potent and selective BPTF inhibitors through structure-guided optimization. These compounds have the potential to inhibit BPTF activity based on experimental results.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Elesha R. Hoffarth, Sunnie Kong, Hai-Yan He, Katherine S. Ryan
Summary: Indolmycin, derived from Streptomyces griseus, is an antibiotic with activity against various pathogens. By utilizing biosynthetic genes in E. coli, researchers were able to synthesize indolmycenic acid, a chiral intermediate leading to the production of indolmycin. Introducing a promiscuous gene expanded structural diversity and allowed for the synthesis of indolmycin derivatives, some of which showed modest antibiotic activity against methicillin-resistant Staphylococcus aureus.
Article
Chemistry, Medicinal
Kaijian Bi, Junfei Cheng, Shipeng He, Yuxin Fang, Min Huang, Chunquan Sheng, Guoqiang Dong
Summary: This study designed and synthesized a series of new von Hippel-Lindau (VHL)-recruiting NAMPT-targeting PROTACs using the proteolysis-targeting chimera (PROTAC) technology. A highly potent NAMPT degrader (B3) was successfully identified, which showed excellent degradation activity and antiproliferative potency against A2780 cells. This study provides a highly effective VHL-recruiting NAMPT degrader for the treatment of ovarian cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Arron Aatkar, Aini Vuorinen, Oliver E. Longfield, Katharine Gilbert, Rachel Peltier-Heap, Craig D. Wagner, Francesca Zappacosta, Katrin Rittinger, Chun-wa Chung, David House, Nicholas C. O. Tomkinson, Jacob T. Bush
Summary: Sulfur(VI) fluorides (SFs) have been used as valuable electrophiles for designing covalent inhibitors that go beyond cysteine and have the potential to broaden the range of liganded proteome. By targeting nucleophilic amino acids, SFs provide a method for covalent protein modification without the need for a nearby cysteine residue. Libraries of reactive fragments containing SFs offer an innovative approach for ligand and tool discovery through mass spectrometry analysis. This study presents a screening approach that utilizes the unique properties of SFs, successfully identifying hit compounds for CAII and BCL6 through a direct-to-biology workflow. Further characterization of the most promising hits includes determining covalent modification sites, kinetics, and target engagement in cells, as well as a detailed molecular understanding through crystallography. This screening protocol holds potential for accelerated discovery of covalent inhibitors beyond cysteine.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Hong-Ping Zhu, Jinlong Chai, Rui Qin, Hai-Jun Leng, Xiang Wen, Cheng Peng, Gu He, Bo Han
Summary: SMYD3 is a histone methyltransferase involved in transcriptional regulation and its overexpression in cancer suggests that inhibiting SMYD3 functions can be a novel therapeutic strategy. In this study, a series of novel tetrahydrofuranyl spirooxindoles were designed and synthesized. The biochemical analysis showed that these inhibitors exhibited good anticancer activity against stomach adenocarcinoma in vitro and in vivo. Mechanistic investigations revealed that compound 7r acted by suppressing Akt methylation and activation by SMYD3 and inhibiting autophagic flux via the Akt-mTOR pathway.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Atukuri Dorababu
Summary: Alzheimer's disease is a neurodegenerative disease with increasing morbidity and mortality worldwide, the complex etiology of which poses challenges for prevention and treatment. Research focusing on discovering efficient drugs for AD is essential, with heterocyclic compounds playing a crucial role in drug discovery.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Jingyi Yang, Xiaoyuan Lin, Na Xing, Zhao Zhang, Haiwei Zhang, Haibo Wu, Weiwei Xue
Summary: The study introduced a multiple conformation-based virtual screening strategy to discover inhibitors targeting SARS-CoV-2 M-pro, identifying potential drug candidates through ensemble docking with a protein mimetics library. Evaluation of the compounds in surface plasmon resonance and fluorescence resonance energy transfer experiments revealed their binding effectiveness and inhibitory properties against M-pro, showing promise as antiviral drug candidates for treating COVID-19.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Agricultural Engineering
Evandro Antonio de Lima, Fernanda Mandelli, Daniel Kolling, Jaqueline Matsusato Souza, Carlos Alberto de Oliveira, Mateus Ribeiro da Silva, Isabelle Lobo de Mesquita Sampaio, Tassia Lopes Junqueira, Mateus Ferreira Chagas, Juliana conceicao Teodoro, Edvaldo Rodrigo de Morais, Mario Tyago Murakami
Summary: This study presents the optimization and scale-up of a bioprocess for enzyme production using an engineered T. reesei strain. The developed bioprocess showed increased productivity and activity, reduced fermentation time, and demonstrated scalability and economic competitiveness. The techno-economic analysis and life-cycle assessment also indicated the potential environmental and cost benefits of this process compared to typical commercial enzymes.
BIORESOURCE TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sarah E. St John, Sakshi Tomar, Shaun R. Stauffer, Andrew D. Mesecar
BIOORGANIC & MEDICINAL CHEMISTRY
(2015)
Article
Chemistry, Medicinal
Arun K. Ghosh, Margherita Brindisi, Yu-Chen Yen, Xiaoming Xu, Xiangping Huang, Thippeswamy Devasamudram, Geoffrey Bilcer, Hui Lei, Gerald Koelsch, Andrew D. Mesecar, Jordan Tang
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2015)
Article
Chemistry, Medicinal
Atul D. Jain, Haranatha Potteti, Benjamin G. Richardson, Laura Kingsley, Julia P. Luciano, Aya F. Ryuzoji, Hyun Lee, Aleksej Krunic, Andrew D. Mesecar, Sekhar P. Reddy, Terry W. Moore
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2015)
Article
Biochemistry & Molecular Biology
Sakshi Tomar, Melanie L. Johnston, Sarah E. St. John, Heather L. Osswald, Prasanth R. Nyalapatla, Lake N. Paul, Arun K. Ghosh, Mark R. Denison, Andrew D. Mesecar
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Virology
Anna M. Mielech, Xufang Deng, Yafang Chen, Eveline Kindler, Dorthea L. Wheeler, Andrew D. Mesecar, Volker Thiel, Stanley Perlman, Susan C. Baker
JOURNAL OF VIROLOGY
(2015)
Article
Biochemistry & Molecular Biology
Nicole M. Hjortland, Andrew D. Mesecar
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2016)
Article
Chemistry, Medicinal
Arun K. Ghosh, Koena Ghosh, Margherita Brindisi, Emma K. Lendy, Yu-Chen Yen, Nagaswamy Kumaragurubaran, Xiangping Huang, Jordan Tang, Andrew D. Mesecar
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Yahira M. Baez-Santos, Scott J. Barraza, Michael W. Wilson, Michael P. Agius, Anna M. Mielech, Nicole M. Davis, Susan C. Baker, Scott D. Larsen, Andrew D. Mesecar
JOURNAL OF MEDICINAL CHEMISTRY
(2014)
Article
Virology
Xufang Deng, E. St. John Sarah, Heather L. Osswald, Amornrat O'Brien, Bridget S. Banach, Katrina Sleeman, Arun K. Ghosh, Andrew D. Mesecar, Susan C. Baker
JOURNAL OF VIROLOGY
(2014)
Article
Virology
Xufang Deng, Sudhakar Agnihothram, Anna M. Mielech, Daniel B. Nichols, Michael W. Wilson, E. St. John Sarah, Scott D. Larsen, Andrew D. Mesecar, Deborah J. Lenschow, Ralph S. Baric, Susan C. Baker
JOURNAL OF VIROLOGY
(2014)
Article
Biochemistry & Molecular Biology
Yu-Chen Yen, Annalissa M. Kammeyer, Jagannadharao Tirlangi, Arun K. Ghosh, Andrew D. Mesecar
Summary: This study developed a platform to produce large amounts of pure BACE2 protein and designed compounds that selectively inhibit BACE1 over BACE2. The research findings could lead to the quicker development of new selective BACE inhibitors for treating Alzheimer's disease or type II diabetes.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
Arun K. Ghosh, Jakka Raghavaiah, Dana Shahabi, Monika Yadav, Brandon J. Anson, Emma K. Lendy, Shin-ichiro Hattori, Nobuyo Higashi-Kuwata, Hiroaki Mitsuya, Andrew D. Mesecar
Summary: This study investigated the synthesis, structure-activity relationship, enzyme inhibition, antiviral activity, and X-ray crystallographic studies of 5-chloropyridinyl indole carboxylate derivatives as potent SARS-CoV-2 chymotrypsin-like protease inhibitors. Compound 1 demonstrated strong inhibitory and antiviral activity, comparable to Remdesivir. Compound 7d showed the most potent enzyme inhibitory activity. X-ray crystal structures of compounds 2, 7b, and 9d bound to SARS-CoV 3CLpro were determined to provide molecular insight into their binding properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
George Minasov, Monica Rosas-Lemus, Ludmilla Shuvalova, Nicole L. Inniss, Joseph S. Brunzelle, Courtney M. Daczkowski, Paul Hoover, Andrew D. Mesecar, Karla J. F. Satchell
Summary: Methylation of viral mRNA caps is essential for translation efficiency, virus replication, and evasion of host cell innate immune responses. The SARS-CoV-2 2'-O-methyltransferase reaction requires divalent cations, preferably Mn2+, and a coronavirus-specific four-residue insert. The unique insert in coronavirus nsp16 alters the capped RNA conformation, making it a potential target for designing selective coronavirus inhibitors.
Article
Chemistry, Medicinal
Samadhi C. Kulathunga, Nicolas M. Morato, Qing Zhou, R. Graham Cooks, Andrew D. Mesecar
Summary: A novel label-free assay based on high-throughput DESI-MS and a fluorometric coupled-enzyme method were developed for quantitation and kinetic analysis of the sulfonation reaction catalyzed by SULT2B1b. Both methods provided consistent kinetic data and indicated the affinity trend of SULT2B1b with its substrates. The DESI-MS assay has promising potential for identifying SULT2B1b inhibitors as prostate cancer therapeutics and can be applied to other drug discovery efforts.