Article
Biochemistry & Molecular Biology
Avelina Lee, Iryna Lebedyeva, Wenbo Zhi, Vani Senthil, Herjot Cheema, Michael W. Brands, Weston Bush, Nevin A. Lambert, Madeline Snipes, Darren D. Browning
Summary: Phosphodiesterase-5 inhibitors (PDE5i) are being studied for their potential in preventing colon cancer. However, their side-effects and interactions with other drugs have been a concern. By modifying the prototypical PDE5i sildenafil, we developed a new analog called malonyl-sildenafil which exhibited reduced lipophilicity and showed promising effects on colon epithelium. This analog suppressed proliferation in the colon epithelium, providing a novel approach to developing a first-in-class drug for colon cancer chemoprevention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Inorganic & Nuclear
Francesca Cutruzzola, Alessandro Paiardini, Chiara Scribani Rossi, Sharon Spizzichino, Alessio Paone, Giorgio Giardina, Serena Rinaldo
Summary: The HD-GYP metalloproteins play a crucial role in regulating bacterial biofilm, motility, and virulence by hydrolyzing cyclic dinucleotides. They exhibit remarkable diversity in active sites, thereby showing different metal ions assisting catalysis.
COORDINATION CHEMISTRY REVIEWS
(2022)
Review
Microbiology
Myles B. Poulin, Laura L. Kuperman
Summary: Bacterial biofilms provide advantages such as adherence, immune evasion, and antibiotic resistance, contributing to a majority of human infections. The signaling molecule c-di-GMP plays a crucial role in the biosynthesis and export of biofilm exopolysaccharides, and targeting this molecule shows promise in treating antibiotic-resistant and biofilm-forming bacteria.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Aileen Jehle, Olga Garaschuk
Summary: Cyclic guanosine monophosphate (cGMP) plays a key role in many important signaling cascades in the body and brain, including phototransduction, olfaction, vasodilation, and functional hyperemia. Recent studies suggest that cGMP may act as a modulator in Alzheimer's disease (AD).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Si Zhang, Jingting Wang, Yu Fan, Wang Meng, Chengqian Qian, Peng Liu, Yi Wei, Chao Yuan, Yuhui Du, Zhiqiu Yin
Summary: Urinary tract infections (UTIs), characterized by recurrence and antibiotic resistance, remain a common health and economic issue. This study focuses on Uropathogenic Escherichia coli (UPEC) and its ability to evade the host immune response through the formation of intracellular bacterial communities (IBCs) in bladder epithelial cells (BECs). The researchers discovered that the small molecule cyclic dimeric guanosine monophosphate (c-di-GMP) and the phosphodiesterase YciR play important roles in this process. They found that YciR enhances the virulence of UPEC by inhibiting the phosphorylation of NF-kappa B.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Chemistry, Medicinal
Ernesto Fedele, Roberta Ricciarelli
Summary: cGMP, a classical second messenger, plays a key role in various physiological functions, particularly in the central nervous system for long-term potentiation. While preclinical studies show potential benefits for cognitive deficits in Alzheimer's disease, clinical studies are still inconclusive at this point.
Review
Medicine, Research & Experimental
Wesam S. Ahmed, Anupriya M. Geethakumari, Kabir H. Biswas
Summary: Phosphodiesterase 5 (PDE5) is a well-studied enzyme that targets cGMP, with therapeutic applications for erectile dysfunction and pulmonary arterial hypertension. Understanding the interaction of PDE5 inhibitors with PDE5 and their structural basis of selectivity is crucial for designing novel drugs.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Cardiac & Cardiovascular Systems
Jie Su, Pierre Coleman, Angeliki Ntorla, Rhys Anderson, Michael J. Shattock, Joseph R. Burgoyne
Summary: This study demonstrates that the cytosolic DNA sensor cGAS can activate PKGI directly through the generation of cGAMP, showing a link between inflammation and blood pressure regulation.
Article
Food Science & Technology
Zhengkai Yi, Jun Yan, Zhaoyang Ding, Jing Xie
Summary: This study explores the regulatory function of HD-GYP domain protein K2227_17660 in spoilage microorganism S. putrefaciens. Deletion of K2227_17660 significantly increased c-di-GMP content, biofilm biomass, extracellular polysaccharide production, trimethylamine and putrescine, and affected membrane fatty acid composition. The results provide new insights into the control of biofilm formation and spoilage potential in S. putrefaciens.
FOOD RESEARCH INTERNATIONAL
(2022)
Article
Cardiac & Cardiovascular Systems
Nicola J. A. Scott, Timothy C. R. Prickett, Christopher J. Charles, Christopher M. Frampton, A. Mark Richards, Miriam T. Rademaker
Summary: This study demonstrates for the first time that combined PDE9 inhibition and NEP inhibition has additional beneficial hemodynamic and renal effects in heart failure. This dual enhancement of NP bioactivity supports PI+NI as a potential therapeutic strategy for heart failure.
JACC-HEART FAILURE
(2023)
Article
Biotechnology & Applied Microbiology
Sonja Koppenhofer, Andrew S. Lang
Summary: The study found that genes encoding proteins with GGDEF, EAL, and HD-GYP domains show different genomic patterns in bacteria. These genes are closely related to the cell cycle and the synthesis and hydrolysis of c-di-GMP.
Review
Cell Biology
Zhilei Wang, Nian Chen, Zhiyong Li, Guang Xu, Xiaoyan Zhan, Jianyuan Tang, Xiaohe Xiao, Zhaofang Bai
Summary: Inflammation is a protective response regulated by the host, with cGAS-STING pathway playing a crucial role in immune defense, viral infections, fatty liver, and cancer metastasis. The potential impact of this pathway in liver diseases has attracted widespread attention, with pharmacological agonists and antagonists offering new therapeutic possibilities. Understanding the mechanisms of cGAS-STING pathway may lead to the development of effective treatments for liver diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Chemical
Hang Chen, Yucheng Tian, Zekun Hu, Cenchao Wang, Peiran Xie, Liping Chen, Fan Yang, Yunyao Liang, Chunyan Mu, Chaohai Wei, Yen-Peng Ting, Guanglei Qiu, Yonghui Song
Summary: This study reveals the key role of bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) in membrane biofouling process in membrane bioreactor (MBR). The high intracellular c-di-GMP levels in membrane foulants were strongly correlated to elevated extracellular polymeric substances (EPS) contents, leading to accelerated membrane fouling rates. The enrichment of specific bacteria related to c-di-GMP and their stronger c-di-GMP metabolic abilities in membrane foulants highlight the importance of c-di-GMP second-messenger pathway in regulating EPS production and governing the membrane biofouling process.
JOURNAL OF MEMBRANE SCIENCE
(2022)
Review
Hematology
Anisa Degjoni, Federica Campolo, Lucia Stefanini, Mary Anna Venneri
Summary: Platelets play a crucial role in the blood circulation system, but their uncontrolled activation can lead to thrombosis. Nitric oxide released by the endothelium stimulates guanylyl cyclase to produce cGMP, which inhibits platelet activation and has therapeutic potential in cardiovascular diseases. Phosphodiesterase type 5 inhibitors show promise in inhibiting platelet aggregation and may have beneficial effects in treating various conditions when combined with nitric oxide donors.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Chemistry, Applied
Oswaldo Perez, Nicolaas Schipper, Martin Bollmark
Summary: The synthesis of the cyclic guanosine monophosphorothioate analogue 1a was achieved through a diastereoselective route, utilizing a silyl protection sequence to achieve high selectivity for the desired product. This chromatography-free process allowed for a successful scale-up production of the compound.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Chemistry, Inorganic & Nuclear
Saumen Chakraborty, Julian Reed, J. Timothy Sage, Nicole C. Branagan, Igor D. Petrik, Kyle D. Miner, Michael Y. Hu, Jiyong Zhao, E. Ercan Alp, Yi Lu
INORGANIC CHEMISTRY
(2015)
Article
Chemistry, Multidisciplinary
Kyle D. Miner, Arnab Mukherjee, Yi-Gui Gao, Eric L. Null, Igor D. Petrik, Xuan Zhao, Natasha Yeung, Howard Robinson, Yi Lu
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2012)
Article
Biochemistry & Molecular Biology
Takahiro Hayashi, Kyle D. Miner, Natasha Yeung, Ying-Wu Lin, Yi Lu, Pierre Moenne-Loccoz
Article
Biochemistry & Molecular Biology
Kyle D. Miner, Thomas D. Pfister, Parisa Hosseinzadeh, Nadime Karaduman, Lynda J. Donald, Peter C. Loewen, Yi Lu, Anabella Ivancich
Article
Chemistry, Multidisciplinary
Ying-Wu Lin, Natasha Yeung, Yi-Gui Gao, Kyle D. Miner, Lanyu Lei, Howard Robinson, Yi Lu
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2010)
Article
Chemistry, Multidisciplinary
Yang Yu, Arnab Mukherjee, Mark J. Nilges, Parisa Hosseinzadeh, Kyle D. Miner, Yi Lu
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2014)
Article
Multidisciplinary Sciences
Natasha Yeung, Ying-Wu Lin, Yi-Gui Gao, Xuan Zhao, Brandy S. Russell, Lanyu Lei, Kyle D. Miner, Howard Robinson, Yi Lu