Article
Chemistry, Multidisciplinary
Wei Wang, Xuan Wang, Guanghui Tang, Chengjun Zhu, Menghua Xiang, Qicai Xiao, Zhi-Min Zhang, Liqian Gao, Shao Q. Yao
Summary: Here, a salicylaldehyde-based reversible covalent inhibitor (A2) with moderate cellular activity against AURKA and prolonged residence time is reported. The inhibitor also shows significant non-covalent inhibition towards LRRK2. This multitarget kinase inhibitor may serve as a starting point for developing more potent, selective, and dual-targeting covalent kinase inhibitors against AURKA and LRRK2 for mitophagy.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Julie E. Bolding, Pablo Martin-Gago, Nima Rajabi, Luke F. Gamon, Tobias N. Hansen, Christian R. O. Bartling, Kristian Stromgaard, Michael J. Davies, Christian A. Olsen
Summary: This study demonstrates the use of aryl fluorosulfate electrophiles as covalent inhibitors targeting SIRT5, providing a potential avenue for the development of drug candidates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biotechnology & Applied Microbiology
Chang-Long Li, Hao-Zhe Ruan, Li-Ming Liu, Wei-Guo Zhang, Jian-Zhong Xu
Summary: This study successfully engineered Corynebacterium glutamicum to efficiently produce L-lysine from starch using a combined method of classical breeding and genome breeding. By introducing amylolytic enzymes and co-expressing them, the production of L-lysine was significantly increased.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jordan J. Aoyama, Gisela Storz
Summary: RNAs can have dual functions, serving as both coding and non-coding molecules. The mechanisms of action and cellular roles of these dual-function RNAs are discussed, along with the competition or synergy between coding and RNA activity. The evolution and potential discovery of more dual-function RNAs are also explored.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Instruments & Instrumentation
Takeshi Uemura, Shunsuke Fujii, Hiroki Yamazaki, Tetsuji Itoh, Kouji Masumoto, Seiichi Nishizawa
Summary: This article introduces an electrochemical biosensor for measuring lysine concentration in blood. The sensor has a simple design and provides rapid measurement, making it valuable for clinical practice. Furthermore, it is versatile and can be used for detecting other amino acids, increasing its practicality.
SENSORS AND MATERIALS
(2022)
Article
Agriculture, Dairy & Animal Science
Bryce Bitsie, Erin Kay Ison, Leah Parker Jenkins, Rebecca Klopp, Conor McCabe, Kayla Mills, Griffin Nicholls, Andrew Richards, Larissa Shirley, Kelsey Teeple, Allan P. Schinckel, Angela Kwon, Kara R. Stewart, Amber Jannasch, Aridany Suarez-Trujillo, Theresa M. Casey
Summary: The early nutritional environment of female animals has an impact on their lactating ability as adults, with the level of colostrum intake affecting mammary development and DNA synthetic rate. Higher levels of lysine in the perinatal period favored cell division over differentiation in the mammary glands of neonatal pigs. Further research is required to explore these relationships.
Article
Biochemistry & Molecular Biology
Binfen Chen, Xinmei Yu, Ting Gao, Yaoyao Wu, Xiaojun Zhang, Sanshu Li
Summary: Aptamers are RNA or DNA molecules that can bind to ligands and have various applications such as biosensors, diagnostic tools, and therapeutic agents. The traditional method of selecting aptamers and integrating an expression platform has limitations, but this study introduces the use of allosteric DNAzymes known as aptazymes to overcome these drawbacks. The researchers used the Expression-SELEX technique to select aptazymes specifically activated by low concentrations of l-phenylalanine. Three aptazymes were characterized and found to have a high affinity for l-phenylalanine, improved catalytic rate in its presence, and the ability to discriminate against similar analogs. This work demonstrates the effectiveness of Expression-SELEX in enriching high-quality ligand-responsive aptazymes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Medicinal
Jesus R. Medina, Xinrong Tian, William H. Li, Dominic Suarez, James F. Mack, Louis LaFrance, Cuthbert Martyr, James Brackley, Christina Di Marco, Ralph Rivero, Dirk A. Heerding, Charles McHugh, Elisabeth Minthorn, Aishwarya Bhaskar, Jacob Rubin, Michael Butticello, Christopher Carpenter, Eldridge N. Nartey, Thomas J. Berrodin, Lorena A. Kallal, Biju Mangatt
Summary: The study identified an indirect strategy to target c-MYC and successfully discovered a series of compounds with c-MYC reducing effects. Through the medicinal chemistry program, the research team identified orally bioavailable potent c-MYC-reducing compounds. The study also developed a minimum pharmacophore model and a property-based approach to modulate pharmacokinetics properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Peiyu Wang, Renwu Zhou, Rusen Zhou, Wenshao Li, Janith Weerasinghe, Shuxiong Chen, Bernd H. A. Rehm, Liqian Zhao, Francesca D. Frentiu, Zhifa Zhang, Kexin Yan, Mary Lor, Andreas Suhrbier, Derek J. Richard, Erik W. Thompson, Kostya Ken Ostrikov, Xiaofeng Dai
Summary: Cold atmospheric plasma (CAP) can effectively inhibit the entry of SARS-CoV-2 into cells and induce nuclear translocation of the virus receptor ACE2. This study provides support for the development of products utilizing CAP to prevent viruses like SARS-CoV-2.
Article
Oncology
Dana C. Borcherding, Eric R. Hugo, Sejal R. Fox, Eric M. Jacobson, Brian G. Hunt, Edward J. Merino, Nira Ben-Jonathan
Summary: This study describes the use of high throughput screening to identify novel small molecules that block the prolactin receptor and suppress breast cancer cell growth, demonstrating their potential as effective therapeutics for breast cancer patients.
Article
Pharmacology & Pharmacy
Valerie Isabella Charlotte Rebhahn, Endre Kiss, Doris Marko, Giorgia Del Favero
Summary: This study compared two intestinal cell models and found that exogenous or endogenous molecules can shape intestinal mechanotransduction by regulating cholesterol homeostasis and plasma membrane architecture, thereby affecting the biomechanical compliance of intestinal cells.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Griffin M. Schroeder, Chapin E. Cavender, Maya E. Blau, Jermaine L. Jenkins, David H. Mathews, Joseph E. Wedekind
Summary: Riboswitches are non-coding RNAs that regulate gene expression in bacteria by recognizing specific cellular effectors. This study reveals the crystal structure of a preQ(1)-sensing riboswitch, showing two effectors stacked in a single binding pocket. The recognition of stacked effectors expands the effector recognition capabilities of riboswitches and has implications for antimicrobial development.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Kaiqi Long, Han Han, Weirong Kang, Wen Lv, Lang Wang, Yufeng Wang, Liang Ge, Weiping Wang
Summary: Photoresponsive drug delivery using red light to trigger one-photon upconversion-like photolysis for cancer therapy has been successfully demonstrated. The nanoparticles protected the photolysis process from oxygen quenching, resulting in efficient drug release upon red light irradiation. The red light-triggered drug release system showed promising anti-tumor efficacy in both in vitro and in vivo experiments, providing a practical reference for future photoresponsive nanocarrier development.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jiawei Zhang, Xueli Hou, Zhang Chen, Yeonjin Ko, Mark W. Ruszczycky, Yutian Chen, Jiahai Zhou, Hung-wen Liu
Summary: This study reports a new twitch radical SAM enzyme, SpeY, that catalyzes a key step in the synthesis of spectinomycin. Through analysis of the reaction products and enzyme structure, the mechanism and catalytic site of the reaction are revealed.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Houda G. Khaled, Hongxuan Feng, Xin Hu, Xin Sun, Wang Zheng, Pan P. Li, Dobrila D. Rudnicki, Wenjuan Ye, Yu-Chi Chen, Noel Southall, Juan Marugan, Christopher A. Ross, Marc Ferrer, Mark J. Henderson, Russell L. Margolis
Summary: The study identified 898 potentially effective compounds for modifying HTT and HTT-AS promoter activity. However, challenges remain in finding a small molecule approach for HTT suppression without affecting cell viability.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Luke T. Nelson, Ryan J. Paxman, Jin Xu, Bill Webb, Evan T. Powers, Jeffery W. Kelly
Summary: The research indicates that the drug candidates AG10, tolcapone, diflunisal, and tafamidis exhibit similar kinetic stabilization at specific concentrations, with differences in safety, absorption and metabolism, pharmacokinetics, and tissue distribution becoming important factors for clinical use decisions regarding kinetic stabilizers.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2021)
Letter
Biochemistry & Molecular Biology
Jeffery Kelly, Evan Powers
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2021)
Article
Neurosciences
Dorit Trudler, Sara Sanz-Blasco, Yvonne S. Eisele, Swagata Ghatak, Karthik Bodhinathan, Mohd Waseem Akhtar, William P. Lynch, Juan C. Pina-Crespo, Maria Talantova, Jeffery W. Kelly, Stuart A. Lipton
Summary: In Parkinson's disease, synaptic and neuronal loss are prominent features. The study reveals that alpha Syn oligomers induce excessive glutamate release from astrocytes, activating NMDARs on neurons and leading to synaptic damage. However, the drug NitroSynapsin shows promise in protecting synapses from alpha Syn-induced damage.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Jeffery W. Kelly
Summary: Pharmacological evidence from clinical trials suggests that protein aggregation plays a key role in tissue degeneration in systemic amyloid diseases, with ongoing investigations focusing on the protein aggregate structures driving tissue pathology and the similarities in etiology between these diseases and Alzheimer's disease.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Review
Chemistry, Medicinal
Arianna Burton, Adam Castano, Marianna Bruno, Steve Riley, Jennifer Schumacher, Marla B. Sultan, Sandi See Tai, Daniel P. Judge, Jignesh K. Patel, Jeffery W. Kelly
Summary: Rare diseases are considered a global public health priority, with Tafamidis representing a major breakthrough in the treatment of transthyretin amyloidosis after decades of research and clinical trials that established its safety and efficacy.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Jessica D. Rosarda, Kelsey R. Baron, Kayla Nutsch, Gabriel M. Kline, Caroline Stanton, Jeffery W. Kelly, Michael J. Bollong, R. Luke Wiseman
Summary: Research has shown that the small molecule proteostasis regulator AA147 can protect against glutamate-induced cell death in neuronal-derived cell culture models. This protective effect is primarily mediated through the activation of the NRF2-regulated oxidative stress response, rather than the ATF6 pathway. These findings highlight the potential of metabolically activated proteostasis regulators like AA147 to activate both protective ATF6 and NRF2 signaling pathways to mitigate oxidative damage associated with various neurological diseases.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fabrizio Chiti, Jeffery W. Kelly
Summary: Protein misfolding diseases are caused by structural abnormalities in proteins, and specific small molecules have been approved to stabilize the folded state of these proteins, providing a promising approach to treat such diseases.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Heike Kroeger, Julia M. D. Grandjean, Wei-Chieh Jerry Chiang, Daphne D. Bindels, Rebecca Mastey, Jennifer Okalova, Amanda Nguyen, Evan T. Powers, Jeffery W. Kelly, Neil J. Grimsey, Michel Michaelides, Joseph Carroll, R. Luke Wiseman, Jonathan H. Lin
Summary: ER stress and UPR signaling contribute to human diseases, including severe congenital vision loss conditions like achromatopsia. Loss-of-function ATF6 variants lead to defective cone formation in the retina, highlighting the essential role of ATF6 in human cone development. Pharmacologic targeting of the ATF6 pathway may hold potential for treating blinding retinal diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Nicholas L. Yan, Reji Nair, Alan Chu, Ian A. Wilson, Kristen A. Johnson, Gareth J. Morgan, Jeffery W. Kelly
Summary: This study investigates the potential of finding small molecule kinetic stabilizers in immunoglobulin light chain amyloidosis, identifying coumarin-based compounds with potential therapeutic effects. Structural-activity relationship data reveals that these compounds bind at different sites in the LC dimer, exerting unique stabilizing effects on LCs.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Gabriel M. Kline, Karina Nugroho, Jeffery W. Kelly
Summary: In this review, we examine the application of Inverse Drug Discovery method using organic compounds of intermediate complexity harboring Sulfur(VI)-fluoride exchange (SuFEx) electrophiles to expand the cellular proteins that can be targeted covalently.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Meng Wang, Edmund Cotter, Ya-Juan Wang, Xu Fu, Angela L. Whittsette, Joseph W. Lynch, R. Luke Wiseman, Jeffery W. Kelly, Angelo Keramidas, Ting-Wei Mu
Summary: This study demonstrates that pharmacologically enhancing endoplasmic reticulum (ER) proteostasis can increase the assembly, trafficking, and surface expression of variant GABA(A) receptors, offering a potential opportunity to mitigate pathology associated with genetic epilepsy and other disease-associated variant ion channels.
CELL AND BIOSCIENCE
(2022)
Article
Cell Biology
Jaleh S. Mesgarzadeh, Isabelle C. Romine, Ethan M. Smith-Cohen, Julia M. D. Grandjean, Jeffery W. Kelly, Joseph C. Genereux, R. Luke Wiseman
Summary: This study identified ER proteostasis factors involved in ATF6-dependent reductions in destabilized TTR secretion through a mass-spectrometry-based interactomics approach. Activation of ATF6 reduces the secretion and subsequent aggregation of amyloidogenic TTR through increased interactions with ATF6-regulated ER proteostasis factors including BiP and PDIA4. PDIA4 retains destabilized TTR in the ER through a redox-independent mechanism. These findings provide a mechanistic basis for the therapeutic targeting of ATF6 activation to improve treatments for TTR-related amyloid diseases.
Article
Geriatrics & Gerontology
Mathew S. Maurer, Dia Smiley, Eli Simsolo, Fabrizio Remotti, Angela Bustamante, Sergio Teruya, Stephen Helmke, Andrew J. Einstein, Ronald Lehman, Jon T. Giles, Jeffery W. Kelly, Felix Tsai, William S. Blaner, Pierre-Jacques Brun, Ron Riesenburger, James Kryzanski, Cindy Varga, Ayan R. Patel
Summary: Lumbar spinal stenosis (LSS) is a common reason for spine surgery in older adults, with amyloid detected in over one third of patients, especially in those over 75 years old. Age, clinical symptoms, cardiac biomarkers, and other parameters did not differ significantly between patients with and without amyloid.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Cecilia Monteiro, Jaleh S. Mesgarzadeh, Joao Anselmo, Joana Fernandes, Marta Novais, Carla Rodrigues, David L. Powers, Evan T. Powers, Teresa Coelho, Jeffery W. Kelly
Summary: This study explored the relationship between TTR stabilization markers and clinical efficacy of tafamidis treatment. The results showed an increase in native TTR concentration and a decrease in non-native TTR concentration. However, changes in native and non-native TTR levels were not correlated with clinical response to tafamidis. Successful tafamidis therapy requires moderate TTR stabilization, and male patients may benefit from higher doses of tafamidis.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Felix J. J. Tsai, Luke T. T. Nelson, Gabriel M. M. Kline, Marcus Jager, John L. L. Berk, Yoshiki Sekijima, Evan T. T. Powers, Jeffery W. Kelly
Summary: This study investigated the plasma concentrations of diflunisal and its efficacy in treating TTR polyneuropathy, finding that at a certain concentration, diflunisal can effectively slow down TTR dissociation rate and inhibit aggregation.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)