Methionine aminopeptidases (MetAPs) are an important class of enzymes that work co-translationally for the removal of initiator methionine. Chemical inhibition or gene knockdown is lethal to the microbes suggesting that they can be used as antibiotic targets. However, sequence and structural similarity between the microbial and host MetAPs has been a challenge in the identification of selective inhibitors. In this study, we have analyzed several thousands of MetAP sequences and established a pattern of variation in the S1 pocket of the enzyme. Based on this knowledge, we have designed a library of 17 azaindole based hydroxamic acid derivatives which selectively inhibited the MetAP from H. pylori compared to the human counterpart. Structural studies provided the molecular basis for the selectivity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bioorg.2021.105185 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Chiang Mai University/Neurophysiology Unit/Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai, Thailand.
Background: Our studies suggest that iron-overloaded rats developed neurotoxicity and cognitive impairment (1,2). An increase in brain mitochondrial fission and brain mitophagy have been considered as one of underlying mechanisms in brain with iron-overloaded condition (3,4). Hence, a pharmacological intervention focused on preventing brain mitochondrial pathologies is required.
View Article and Find Full Text PDFBackground: In Alzheimer's disease (AD), histone acetylation is disrupted, suggesting loss of transcriptional control. Moreover, converging evidence suggests an age- and AD-dependent loss of transcription controlled by all-trans-retinoic acid (ATRA), the bioactive metabolite of vitamin A (VA). Antioxidant depletion causes oxidative stress (OS).
View Article and Find Full Text PDFPreclinical Assessment of Safety and Efficacy of Deferoxamine (DFO)-pretreated Feline Adipose Mesenchymal Stem Cells.
In Vivo
December 2024
Department of Veterinary Medicine, Yanbian University, Yanji, P.R. China;
Background/aim: This study aimed to investigate the safety and efficacy of deferoxamine (DFO) pretreated feline adipose tissue derived mesenchymal stem cells (fATMSCs) for the treatment of inflammatory disorders.
Materials And Methods: fATMSCs were isolated from feline adipose tissue and characterized using flow cytometry for surface marker expression and differentiation assays for adipogenic, osteogenic, and chondrogenic lineages. Different concentrations of DFO were used to evaluate its impact on fATMSC activity.
Discovery of novel TACE inhibitors using graph convolutional network, molecular docking, molecular dynamics simulation, and Biological evaluation.
PLoS One
December 2024
Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon, Republic of Korea.
The increasing utilization of deep learning models in drug repositioning has proven to be highly efficient and effective. In this study, we employed an integrated deep-learning model followed by traditional drug screening approach to screen a library of FDA-approved drugs, aiming to identify novel inhibitors targeting the TNF-α converting enzyme (TACE). TACE, also known as ADAM17, plays a crucial role in the inflammatory response by converting pro-TNF-α to its active soluble form and cleaving other inflammatory mediators, making it a promising target for therapeutic intervention in diseases such as rheumatoid arthritis.
View Article and Find Full Text PDFDesign, Synthesis, and Evaluation of Novel (-)-cis-N-Normetazocine Derivatives: In Vitro and Molecular Modeling Insights.
Chem Biol Drug Des
December 2024
Department of Drug and Health Sciences, University of Catania, Catania, Italy.
Suitable structural modifications of the functional groups at N-substituent of (-)-cis-N-normetazocine nucleus modulate the affinity and activity profile of related ligands toward opioid receptors. Our research group has developed several compounds and the most interesting ligands, LP1 and LP2, exhibited a dual-target profile for mu-opioid receptor (MOR) and delta-opioid receptor (DOR). Recent structure-affinity relationship studies led to the discovery of novel LP2 analogs (compounds 1 and 2), which demonstrated high MOR affinity in the nanomolar range.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!