Article
Chemistry, Medicinal
Laura A. T. Cleghorn, Richard J. Wall, Seibastien Albrecht, Stuart A. MacGowan, Suzanne Norval, Manu De Rycker, Andrew Woodland, Daniel Spinks, Stephen Thompson, Stephen Patterson, Victoriano Corpas Lopez, Gourav Dey, Iain T. Collie, Irene Hallyburton, Robert Kime, Frederick R. C. Simeons, Laste Stojanovski, Julie A. Frearson, Paul G. Wyatt, Kevin D. Read, Ian H. Gilbert, Susan Wyllie
Summary: Despite advancements in treatment options, there is a need for new drugs to eradicate human African trypanosomiasis (HAT). In this study, potent 2,4-diaminothiazoles were developed as drug-like inhibitors against Trypanosoma brucei. Animal testing confirmed the efficacy in the hemolymphatic stage, but optimization for brain penetration did not achieve the desired in vivo efficacy due to a shift in mechanism of action. Subsequent studies identified a nonessential kinase as the target and emphasized the importance of cytotoxic drugs for HAT treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Polymer Science
Vitor Lobo, Ashly Rocha, Tarsila G. G. Castro, Maria Alice Carvalho
Summary: The phosphatidylinositol-3 kinase (PI3K) pathway is commonly activated in various cancers, and there has been a growing interest in finding selective inhibitors for the four isoforms of PI3K. A drug design strategy was employed to create a virtual library of 105 compounds, comparing the isoforms and designing new derivatives based on a known active scaffold. The screening of the library led to the identification of 19 selective inhibitors for PI3Ka and PI3K?, and further analysis established correlations between affinity data and physicochemical properties.
Article
Chemistry, Multidisciplinary
Aishwarya Vetrivel, Santhi Natchimuthu, Vidyalakshmi Subramanian, Rajeswari Murugesan
Summary: Pseudomonas aeruginosa, an opportunistic pathogen, utilizes quorum sensing to promote biofilm formation and virulent gene expression. In this study, high-throughput virtual screening identified three potential LasR inhibitors as promising candidates for treating P. aeruginosa infections. Molecular dynamics simulation confirmed the stable interaction between these compounds and the target protein LasR, validating their potential as quorum sensing inhibitors.
Article
Biochemistry & Molecular Biology
James Adams, Benjamin P. Thornton, Lydia Tabernero
Summary: The study identified unique ligand cluster distributions specific to kinase interaction motif protein tyrosine phosphatases (KIM-PTPs) and found that ligand clusters coincide with functional and substrate binding sites in these PTPs. Ligand efficiency index (LEI) analysis showed that binders in these clusters reside in a more drug-like chemical-biological space. Differences in clusters across all KIM-PTPs highlight a distinct and specific profile for each phosphatase, with potential for exploiting unexplored allosteric functional sites for drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Xueting Qiu, Xuben Hou, Yue Yang, Hao Fang, Fei Cui, Xinying Yang
Summary: In this study, a new method based on electrophoretically mediated microanalysis was developed for the investigation of PTPRO enzymatic activity. The method was successfully used to determine the kinetics of PTPRO and the inhibitory concentration of PTPRO inhibitors. The method exhibited improved accuracy and reduced consumption compared to traditional methods.
JOURNAL OF CHROMATOGRAPHY A
(2024)
Article
Biochemistry & Molecular Biology
Aathithya Diaz, G. Shripushkar, Shruti Balaji, Jayapradha Ramakrishnan, Subbiah Thamotharan, Vigneshwar Ramakrishnan
Summary: The emergence of antibiotic resistance is a major global threat in healthcare. This study aims to identify potent inhibitors for the B1 subclass of Metallo-beta-Lactamases (MBL) from marine metabolites. Through in silico approaches, potential inhibitors were identified, including N-methyl mycosporine-Ser, makaluvic acid and didymellamide. The study highlights the importance of multiple in silico approaches and reveals promising inhibitors that can be found in marine systems.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biology
Ammar D. Elmezayen, Yelekci Kemal
Summary: The fundamental cause of human cancer is strongly influenced by epigenetic factors, with research focusing on identifying isoform-selective inhibitors against specific HDACs through structure-based drug design. The top-ranked inhibitors showed high binding affinity and isoform selectivity, making them potential drug candidates for further optimization towards designing safe isoform-selective HDAC inhibitors.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2021)
Review
Education & Educational Research
Yen-Fen Lee, Gwo-Jen Hwang, Pei-Ying Chen
Summary: An after-class review approach with an AI-based chatbot is proposed in this study to provide students with immediate and quality feedback during the learning process. The research results show that the application of AI-based chatbots can improve students' academic performance, self-efficacy, learning attitude, and motivation.
ETR&D-EDUCATIONAL TECHNOLOGY RESEARCH AND DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Marko Jukic, Rodolphe Auger, Victor Folcher, Matic Proj, Helene Barreteau, Stanislav Gobec, Thierry Touze
Summary: The study identified small molecules that inhibit the activity of BacA, an enzyme involved in the recycling of undecaprenyl pyrophosphate. The compounds showed significant inhibition of the enzyme's activity and also demonstrated antibacterial activity against Escherichia coli strains.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Public, Environmental & Occupational Health
Ruyue Liu, Qiuxia Li, Yifan Li, Wenjian Wei, Siqi Ma, Jialin Wang, Nan Zhang
Summary: The morbidity and mortality of patients with upper gastrointestinal cancer (UGC) are increasing rapidly in high-incidence countries in Asia, which has raised concerns for public health. Screening can effectively reduce the incidence and mortality of UGC, but the low population uptake rate affects the screening effect.
JMIR PUBLIC HEALTH AND SURVEILLANCE
(2023)
Article
Biology
Jingyu Zhu, Haoer Zhang, Lei Jia, Lijun Ma, Lei Xu, Yun Chen, Yanfei Cai, Huazhong Li, Gang Huang, Jian Jin
Summary: This study focuses on developing novel PNKP kinase inhibitors through molecular docking based virtual screening with multiple PNKP conformations integrating homology modeling, molecular dynamics simulation, and binding free energy calculation. The top-scored molecule was further analyzed using molecular dynamics simulation to reveal the binding mechanism with PNKP, providing guidance for the development of PNKP kinase inhibitors.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Neelesh Maheshwari, Chandrabose Karthikeyan, Shraddha Bhadada, Amit K. Verma, Chan-dan Sahi, N. S. Hari Narayana Moorthy, Piyush Trivedi
Summary: This study successfully developed novel PTP1B inhibitors with good enzyme binding affinity and activity through computational methods and biological evaluation studies. The identified compounds showed significant interactions with the active site residues of the PTP1B enzyme, with compounds S1 and S2 exhibiting considerable in vitro PTP1B inhibitory and in vivo antidiabetic activities.
LETTERS IN DRUG DESIGN & DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Marko Jukic, Dusanka Janezic, Urban Bren
Summary: In this study, a novel class of potential SARS-CoV-2 RdRp inhibitors was identified through in silico high-throughput virtual screening, providing clues for the development of new drugs for treating COVID-19. These compounds showed favorable binding free energies in molecular dynamics simulations, with potential for in vitro biological evaluation and mode of action studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Audiology & Speech-Language Pathology
Jacqueline K. Bezuidenhout, Katijah Khoza-Shangase, Tim De Maayer, Renate Strehlau
Summary: The study conducted in an academic secondary hospital in Johannesburg, South Africa, found that the majority of neonates were screened within the first 24 hours of life. A high refer rate was observed in DPOAE screening, with no significant association found between maternal or neonatal risk factors and refer findings. These findings suggest implications for successful implementation of NHS programmes in South Africa, emphasizing the importance of screening timing and protocol measures.
SOUTH AFRICAN JOURNAL OF COMMUNICATION DISORDERS
(2021)
Article
Chemistry, Applied
Navidha Aggarwal, Sandeep Jain, Neetu Chopra
Summary: A new series of thiazolidin-4-one analogs with thiadiazole derivative was synthesized using propanoic acid and thiosemicarbazide. The structures of the synthesized compounds were validated using spectral techniques. The in vitro acetylcholinesterase inhibitory activity of these compounds was assessed, and certain compounds showed potent activity, which could be utilized for the development of new AChE inhibitors and further research.
BIOINTERFACE RESEARCH IN APPLIED CHEMISTRY
(2022)
Article
Dermatology
Jun Cui, Qian Zhao, Zhongya Song, Zhiming Chen, Xin Zeng, Chu Wang, Zhimiao Lin, Fengchao Wang, Yong Yang
Summary: In this study, researchers found that KLHL24 plays a role in regulating hair maintenance by mediating the stability of keratin 15, an intermediate filament that composes the hair follicle stem cell cytoskeleton network. KLHL24 variants cause a decrease in keratin 15, leading to hair loss.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Fan Yang, Guogeng Jia, Jiuzhou Guo, Yuan Liu, Chu Wang
Summary: Activity-based protein profiling (ABPP) is a powerful tool for annotating protein functions and discovering targets of bioactive ligands. In this study, we combined data-independent acquisition (DIA) MS with ABPP to develop a label-free quantitative chemical proteomic method called DIA-ABPP. With good reproducibility and high accuracy, DIA-ABPP allows for high-throughput quantification, enabling comprehensive profiling of functional proteomes and interactions with bioactive small molecules.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Chu Wang, Xing Chen, Fan Yang
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Shuchang Lai, Ying Chen, Fan Yang, Weidi Xiao, Yuan Liu, Chu Wang
Summary: Protein lipoylation is an important post-translational modification related to various human diseases. However, a comprehensive strategy for quantifying lipoylation sites is still lacking. In this study, we developed a novel approach to quantify lipoylation sites in complex biological samples and investigated their functional connection with the synthetic pathway. This research will contribute to the understanding of the molecular mechanisms underlying lipoylation-related diseases.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Xuemin Chen, Yuan Liu, Linghao Kong, Ziyang Wen, Weize Wang, Chu Wang
Summary: A quantitative chemoproteomic platform based on mass shifts was developed to identify protein cross-links induced by MGO in proteomes. 66 cross-linked targets were identified, including components of functional complexes such as spliceosomes and ribosomes. The study also revealed that the active-site Cys331 played a critical role in mediating the cross-linking process.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Analytical
Huan Tang, Guogeng Jia, Jinjun Gao, Fan Yang, Ziyao Tang, Yuan Liu, Chu Wang
Summary: In this paper, a chemical proteomic strategy called SETRIP was developed to quantitatively monitor the turnover dynamics of selenoproteins at the proteomic level. The half-lives of nine selenoproteins were accurately measured, ranging from 6 to 32 hours. The study provides a global portrait of dynamic changes in the selenoproteome and suggests the existence of hierarchy regulation in the turnover of selenoproteins.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yankun Wang, Chu Wang
Summary: This study reveals the dynamic changes of the cysteinome and identifies a sensor switch associated with ferroptosis through a chemical proteomic strategy. It also uncovers a novel functional link between ferroptosis and proteasome-mediated protein degradation.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Biwei Liu, Shentian Zhuang, Runze Tian, Yuan Liu, Yanqi Wang, Xiaoguang Lei, Chu Wang
Summary: Bile acids are endogenous metabolites with important functions. Through chemoproteomic methods, we identified the histidine kinase EnvZ as a novel sensor for bile acids in bacteria. Activation of the downstream signaling pathway mediated by EnvZ helps bacteria tolerate bile acids. This discovery opens new opportunities to combat bile acid-tolerating pathogens.
ACS CHEMICAL BIOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Weidi Xiao, Ying Chen, Chu Wang
Summary: Reactive cysteines play important regulatory roles in proteins and biological processes. The chemoproteomic method isoTOP-ABPP enables global profiling of cysteine reactivity and has been widely applied in reactive cysteinome profiling, ligand discovery, and mechanistic investigation. This review summarizes the history, recent developments, and future directions of chemoproteomic technology in reactive cysteinome profiling.
ISRAEL JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Dongyang Liu, Weidi Xiao, Haoting Li, Yanling Zhang, Shouli Yuan, Chengxi Li, Suwei Dong, Chu Wang
Summary: This study discovered a novel protein post-translational modification called lysine itaconylation, opening up new avenues for investigating the role of itaconate in immunoregulation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Jinjun Gao, Xinlei Sheng, Jianfeng Du, Di Zhang, Chang Han, Yue Chen, Chu Wang, Yingming Zhao
Summary: We developed a new database search strategy called CHiMA, which uses 50% matched fragment ions as the key criterion to identify high-confidence PSMs. Compared to conventional methods, CHiMA identified twice as many histone modification sites in benchmark datasets. Reanalysis of previous proteomics data using CHiMA led to the discovery of 113 new histone marks, almost doubling the number of previously reported marks. This tool not only offers a valuable approach for identifying histone modifications but also greatly expands the repertoire of histone marks.
Article
Biochemical Research Methods
Weidi Xiao, Ying Chen, Jin Zhang, Zhihao Guo, Yihao Hu, Fan Yang, Chu Wang
Summary: The study developed a simplified and ultrafast chemoproteomic analysis method that allows for quick and efficient quantitative analysis of protein activity and modifications. Compared to traditional methods, this approach reduces sample preparation time and enhances the sensitivity and coverage of cysteinome profiling.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Xianghe Wang, Yihai Zhang, Chu Wang
Summary: Cisplatin is a widely used cancer metallodrug that targets DNA and cysteines in proteins to induce cytotoxicity. In this study, a competitive activity-based protein profiling strategy was applied to identify cisplatin-binding cysteines in cancer proteomes. A novel cisplatin target, MetAP1, was discovered and shown to contribute to the cytotoxicity of cisplatin.
RSC CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Tao-Bin He, Bing-Chao Yan, Yuan-Fei Zhou, Yue-Qian Sang, Xiao-Nian Li, Han-Dong Sun, Chu Wang, Xiao-Song Xue, Pema-Tenzin Puno
Summary: This study reported an unprecedented class of cadinane sesquiterpene [4+2] dimers, which were synthesized using a protection-free approach, and revealed the origin of selectivity in the key [4+2] cycloaddition and the mechanism of inhibition of reaction pathway bifurcation. Chemical proteomics results showed that these compounds had multiple targets. This work provides experimental evidence and a powerful strategy for the discovery of novel compounds and exploration of the biological properties of natural products.
Article
Biochemistry & Molecular Biology
Ying Chen, Baiyi Quan, Yuanpei Li, Yuan Liu, Wei Qin, Chu Wang
Summary: Researchers developed a chemoproteomic strategy called STO-MS to accurately quantify the stoichiometry of protein modifications in complex biological samples. They successfully determined the stoichiometry of 197 proteins modified by HNE and shed light on the biological significance of PTMs in oxidative stress.
RSC CHEMICAL BIOLOGY
(2022)