The discovery and initial optimization of a novel anthranilic acid derived class of antibacterial agents which suffered from extensive protein binding has been previously reported. The structure-activity relationships around the carboxylic acid substituent are described herein. This acid was replaced by several alternative functional groups in attempts to retain bioactivity while reducing protein binding. Only groups with an acidic proton retained activity, and analogs containing those groups maintained the protein binding inherent to this class of antibacterial agents.
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http://dx.doi.org/10.1016/j.bmcl.2007.04.074 | DOI Listing |
Viruses
December 2024
Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria.
Protein phosphorylation is a crucial regulatory mechanism in cellular homeostasis. The human cytomegalovirus (HCMV) incorporates protein phosphatase 1 (PP1) into its tegument, yet the biological relevance and mechanisms of this incorporation remain unclear. Our study offers the first characterization of the PP1 interactome during HCMV infection and its alterations.
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December 2024
Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, Taiwan.
This study investigated a library of known and novel glycyrrhizic acid (GL) conjugates with amino acids and dipeptide esters, as inhibitors of the DENV NS2B-NS3 protease. We utilized docking algorithms to evaluate the interactions of these GL derivatives with key residues (His51, Asp75, Ser135, and Gly153) within 10 Å of the DENV-2 NS2B-NS3 protease binding pocket (PDB ID: 2FOM). It was found that compounds and exhibited unique binding patterns, forming hydrogen bonds with Asp75, Tyr150, and Gly153.
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December 2024
Key Laboratory of Biosafety Defense (Naval Medical University), Ministry of Education, Naval Medical University (Second Military Medical University), Shanghai 200433, China.
Unlike other ubiquitin-like family members, UBL5 is structurally and functionally atypical, and a novel role in various biological processes and diseases has been discovered. UBL5 can stabilize the structure of the spliceosome, can promote post-transcriptional processing, and has been implicated in both DNA damage repair and protein unfolding reactions, as well as cellular mechanisms that are frequently exploited by viruses for their own proliferation during viral infections. In addition, UBL5 can inhibit viral infection by binding to the non-structural protein 3 of rice stripe virus and mediating its degradation.
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December 2024
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Chikungunya virus (CHIKV) is an emerging, mosquito-borne arthritic alphavirus increasingly associated with severe neurological sequelae and long-term morbidity. However, there is limited understanding of the crucial host components involved in CHIKV replicase assembly complex formation, and thus virus replication and virulence-determining factors, within the central nervous system (CNS). Furthermore, the majority of CHIKV CNS studies focus on neuronal infection, even though astrocytes represent the main cerebral target.
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December 2024
Department of Biological Sciences, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA.
During virus infection, the activation of the antiviral endoribonuclease, ribonuclease L (RNase L), by a unique ligand 2'-5'-oilgoadenylate (2-5A) causes the cleavage of single-stranded viral and cellular RNA targets, restricting protein synthesis, activating stress response pathways, and promoting cell death to establish broad antiviral effects. The immunostimulatory dsRNA cleavage products of RNase L activity (RL RNAs) recruit diverse dsRNA sensors to activate signaling pathways to amplify interferon (IFN) production and activate inflammasome, but the sensors that promote cell death are not known. In this study, we found that DEAH-box polypeptide 15 (DHX15) and retinoic acid-inducible gene I (Rig-I) are essential for apoptosis induced by RL RNAs and require mitochondrial antiviral signaling (MAVS), c-Jun amino terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) for caspase-3-mediated intrinsic apoptosis.
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