Article
Multidisciplinary Sciences
Wen-juan Li, Yao-hui He, Jing-jing Yang, Guo-sheng Hu, Yi-an Lin, Ting Ran, Bing-ling Peng, Bing-lan Xie, Ming-feng Huang, Xiang Gao, Hai-hua Huang, Helen He Zhu, Feng Ye, Wen Liu
Summary: The study identified numerous substrates for Type I and II arginine methyltransferases and revealed features of PRMT7-regulated methylation, showing it primarily methylates a specific glycine and arginine motif. The study also demonstrated the role of PRMT4/5/7 in cancer-associated splicing regulation and potential as targets for cancer therapy. Pharmacological inhibition of PRMT4/5/7 was shown to suppress cancer cell growth with synergistic effects when co-inhibited.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Ji Hye Kim, Byong Chul Yoo, Woo Seok Yang, Eunji Kim, Sungyoul Hong, Jae Youl Cho
Summary: Cells have developed a sophisticated signaling pathway in response to DNA damage, with protein arginine methylation playing critical roles in modulating DNA repair proteins and maintaining genome integrity. PRMTs can directly methylate DNA repair proteins or deposit methylation marks on histones to regulate various cellular processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Erin K. Webb, Sean Y. Ng, Andrew I. Mikhail, Derek W. Stouth, Tiffany L. Vanlieshout, Anika L. Syroid, Vladimir Ljubicic
Summary: This study investigated the effects of short-term pharmacological inhibition of CARM1 on skeletal muscle. The results showed that CARM1 inhibition did not affect muscle mass but impaired exercise capacity, especially in male mice. Moreover, the morphological and molecular signatures of denervation-induced muscle atrophy were largely maintained in animals administered the CARM1 inhibitor.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Amar Pratap Singh, Rakesh Kumar, Dinesh Gupta
Summary: Human PRMT4, also known as CARM1, is a type I arginine methyltransferase protein. Structural studies reveal the importance of the N-terminal region, Rossman fold, and dimerization arm in PRMT4 activity. Further elucidation is needed on the communication pathways in PRMT4. Molecular dynamics simulations and network analysis show differences in monomeric and dimeric forms of hPRMT4, as well as the existence of communication networks and an allosteric pathway. These findings provide insights into conformational changes, dimerization mechanism, SAM binding, and inhibitor design for hPRMT4.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Oncology
Camille Sauter, John Simonet, Fabien Guidez, Baptiste Dumetier, Baptiste Pernon, Mary Callanan, Jean-Noel Bastie, Romain Aucagne, Laurent Delva
Summary: This review summarizes the role of protein arginine methyltransferases (PRMTs) in blood cell formation and blood cancers. It provides insights into the development of PRMT inhibitors for the treatment of hematological malignancies. By controlling cell differentiation and transcription, PRMTs play a central role in the formation and maturation of blood cells. Inhibiting PRMT activity shows promise in treating hematological malignancies, as demonstrated by preclinical studies and phase I clinical trials.
Article
Neurosciences
Anna L. Gill, Alan S. Premasiri, Fernando G. Vieira
Summary: Hexanucleotide repeat expansion mutations in the C9ORF72 gene contribute to a significant portion of familial ALS and FTD cases, as well as a percentage of sporadic ALS cases. These mutations lead to the production of dipeptide repeat proteins, including cytotoxic polyGR and polyPR. Methylation of arginine residues in polyGR/polyPR may play a role in neurodegeneration processes associated with G4C2(n) mutations.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Cell Biology
Jean-Paul Bryant, John Heiss, Yeshavanth Kumar Banasavadi-Siddegowda
Summary: Protein arginine methylation, a common post-translational modification, plays a pivotal role in cellular regulation and is linked to neurodegenerative diseases, metabolic diseases, and tumor progression. Aberrant expression of PRMTs is associated with the development of brain tumors, leading to investigations of PRMT inhibitors for glioblastoma, medulloblastoma, and other cancers.
Article
Chemistry, Multidisciplinary
Hongyu Guo, Jiaqiao Yang, Jian Zeng, Xiaoqi Yu, Shanshan Yu, Lin Pu
Summary: The first near IR fluorescent probe for chemoselective and enantioselective recognition of arginine in aqueous solution is reported. This probe, consisting of a 1,1'-binaphthyl-based chiral aldehyde unit and a rhodamine-based near IR chromophore, in combination with La3+, shows highly selective fluorescent enhancement with arginine at lambda=764 nm upon excitation at lambda=690 nm. Little or no fluorescence response is observed towards the chirality miss-matched arginine enantiomer or other common amino acids and their enantiomers. This probe also allows visual discrimination of the arginine enantiomers due to its rapid and distinct color change upon interaction with the substrate.
Review
Biochemistry & Molecular Biology
Jian Qin, Jian Xu
Summary: Arginine methylation plays a critical role in regulating EMT, affecting signaling, transcription, and splicing regulation.
Article
Spectroscopy
Sofia A. Zakharenkova, Ekaterina A. Katkova, Irina A. Doroshenko, Anna S. Kriveleva, Aleksandra N. Lebedeva, Tatyana A. Vidinchuk, Anna Shik, Sergei S. Abramchuk, Tatyana A. Podrugina, Mikhail K. Beklemishev
Summary: This study developed sensing schemes without selective receptors by synthesizing carbocyanine dyes and nanoparticles for fluorescence detection, leading to a rapid method for detecting neomycin in urine.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Biochemistry & Molecular Biology
Melody D. Fulton, Tran Dang, Tyler Brown, Y. George Zheng
Summary: This study explores how local changes on adjacent residues in histone substrate regulate the activities of PRMT1 and PRMT5 enzymes. Phosphorylation at H4S1 inhibits the activity of both enzymes, while the presence of a positively charged H4K5 is important for PRMT1 catalysis. Acetylation of H4K5 or loss of the H4K5 epsilon-amine affects the methylation of H4R3.
Article
Hematology
Shelby L. Sloan, Fiona Brown, Mackenzie Long, Christoph Weigel, Shirsha Koirala, Ji-Hyun Chung, Betsy Pray, Lynda Villagomez, Claire Hinterschied, Anuvrat Sircar, Jobeth Helmig-Mason, Alexander Prouty, Eric Brooks, Youssef Youssef, Walter Hanel, Samir Parekh, Wing Keung Chan, Zhengming Chen, Rosa Lapalombella, Lalit Sehgal, Kris Vaddi, Peggy Scherle, Selina Chen-Kiang, Maurizio Di Liberto, Olivier Elemento, Cem Meydan, Jonathan Foox, Daniel Butler, Christopher E. Mason, Robert A. Baiocchi, Lapo Alinari
Summary: Inhibition of PRMT5 in mantle cell lymphoma demonstrated antitumor activity and restored regulatory activity of the cell cycle, apoptotic cell death, and negative regulators of the B-cell receptor-PI3K/AKT signaling pathway. The selective targeting of PRMT5 shows promise as a potential therapy for patients with relapsed/refractory MCL.
Review
Medicine, Research & Experimental
Joanna Janisiak, Patrycja Kopytko, Maciej Tarnowski
Summary: Arginine methylation is a permanent and frequent post-translational modification, with significant impact on chromatin functions and involvement in various biological processes. Dysregulation of PRMT levels may contribute to cancer transformation, and specific PRMT inhibitors show promise in the treatment of oncological diseases.
POSTEPY HIGIENY I MEDYCYNY DOSWIADCZALNEJ
(2021)
Article
Biochemistry & Molecular Biology
Juan A. Leal, Zoila M. Estrada-Tobar, Frederick Wade, Aron Judd P. Mendiola, Alexander Meza, Mariel Mendoza, Paul S. Nerenberg, Cecilia I. Zurita-Lopez
Summary: The study demonstrates that phosphorylation of serine-10 on histone H3 affects arginine-8 methylation by forming a salt bridge and other interactions between neighboring amino acid residues. This inhibits the deposition of neighboring methyl groups through intrapeptide interactions rather than steric hindrance.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Oncology
Mosebo Armstrong Manabile, Rodney Hull, Richard Khanyile, Thulo Molefi, Botle Precious Damane, Nigel Patrick Mongan, David Owen Bates, Zodwa Dlamini
Summary: Colorectal cancer is a leading cause of cancer-related deaths globally, with increasing incidence in developing countries. Dysregulated alternative splicing processes in colorectal cancer can promote its development and progression by producing proteins that activate cancer-promoting genes or deactivate cancer-inhibiting genes. It is important to identify these dysregulated alternative splicing genes in order to develop targeted treatments and diagnostics to stop cancer development and progression.
Article
Biochemical Research Methods
Liza Ngo, Jiang Wu, Chao Yang, Yujun George Zheng
ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
(2015)
Article
Chemistry, Medicinal
Hao Hu, Eric A. Owens, Hairui Su, Leilei Yan, Andrew Levitz, Xinyang Zhao, Maged Henary, Yujun George Zheng
JOURNAL OF MEDICINAL CHEMISTRY
(2015)
Article
Multidisciplinary Sciences
Erik W. Debler, Kanishk Jain, Rebeccah A. Warmack, You Feng, Steven G. Clarke, Guenter Blobel, Pete Stavropoulos
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Article
Biochemistry & Molecular Biology
Jing Zhang, Kun Qian, Chunli Yan, Maomao He, Brenson A. Jassim, Ivaylo Ivanov, Yujun George Zheng
Article
Chemistry, Analytical
Xiangkun Yang, Sean X. Naughton, Zhen Han, Maomao He, Y. George Zheng, Alvin V. Terry, Michael G. Bartlett
ANALYTICAL CHEMISTRY
(2018)
Article
Chemistry, Multidisciplinary
Maomao He, Zhen Han, Jing Qiao, Liza Ngo, May P. Xiong, Y. George Zheng
CHEMICAL COMMUNICATIONS
(2018)
Article
Biochemistry & Molecular Biology
Liza Ngo, Tyler Brown, Yujun G. Zheng
CHEMICAL BIOLOGY & DRUG DESIGN
(2019)
Article
Biochemistry & Molecular Biology
Jiabao Song, Liza Ngo, Kaylyn Bell, Y. George Zheng
Summary: This study demonstrates a new method for studying lysine acetyltransferases (KATs) by using a clickable acyl-CoA reporter to acylate proteins. 123 protein substrates of histone acetyltransferase 1 (HAT1) were discovered, expanding our understanding of this important enzyme.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Subodh Kumar Samrat, Qamar Bashir, Yiding Huang, Carl William Trieshmann, Anil Mathew Tharappel, Ran Zhang, Ke Chen, Y. Geoge Zheng, Zhong Li, Hongmin Li
Summary: This study developed a fluorescence polarization-based high throughput screening (HTS) assay to specifically target the methyltransferase (MTase) and identified two candidate drugs for the treatment of flavivirus infections.
ACS INFECTIOUS DISEASES
(2023)
Review
Biochemistry & Molecular Biology
Tyler Brown, Terry Nguyen, Bo Zhou, Y. George Zheng
Summary: Protein arginine methylation is a common post-translational modification in eukaryotic cells that affects various cellular processes. Aberrant expression and activity of protein arginine methyltransferases (PRMTs) have been observed in many diseases, including cancer. Targeting PRMTs has become an attractive therapeutic strategy. This review highlights the chemical aspects of arginine methylation and the development of chemical tools for studying PRMTs and arginine methylation in biology and disease.
RSC CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kun Qian, Chunli Yan, Hairui Su, Tran Dang, Bo Zhou, Zhenyu Wang, Xinyang Zhao, Ivaylo Ivanov, Meng-Chiao Ho, Y. George Zheng
Summary: PRMTs are crucial epigenetic regulators involved in various human diseases, including cancer. Through virtual screening and enzymatic tests, a new potential anticancer inhibitor K313 was discovered, which exhibited significant inhibitory effects on cell proliferation in leukemia cells by targeting PRMT1.
RSC MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Jeanne N. Hansen, Xingguo Li, Y. George Zheng, Louis T. Lotta, Abhishek Dedhe, Nina F. Schor
ACS CHEMICAL NEUROSCIENCE
(2017)
Article
Biochemistry & Molecular Biology
Melody D. Fulton, Jing Zhang, Maomao He, Meng-Chiao Ho, Y. George Zheng
Article
Biochemistry & Molecular Biology
Zhen Han, Chau-wen Chou, Xiangkun Yang, Michael G. Bartlett, Y. George Zheng
ACS CHEMICAL BIOLOGY
(2017)
Review
Chemistry, Multidisciplinary
Maomao He, Zhen Han, Liang Liu, Y. George Zheng
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2018)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)