From fragments to leads: novel bacterial NAD + -dependent DNA ligase inhibitors

Autor:	Haris Jahic, Kerry E. Murphy-Benenato, P. Ann Boriack-Sjodin, Dan Carcanague, Jenna Harang, Tina Howard, Claire Brassington, Madhusudhan Reddy Gowravaram, Charles J. Eyermann, Lakshmaiah Gingipalli, Herbert Oguto, Sahil Patel, Robert A. Giacobbe, Ludovic Otterbein, Amy Kutschke, James T. Loch, Georgine Ioannidis, Valerie A. Laganas, Michael R. Hale, Adam B. Shapiro, Kevin J. Embrey, Matthew D. Miller
Rok vydání:	2015
Předmět:	chemistry.chemical_classification DNA ligase biology Organic Chemistry biology.organism_classification Biochemistry Adenosine chemistry.chemical_compound Enzyme chemistry Drug Discovery medicine NAD+ kinase Binding site LIGA DNA Bacteria medicine.drug
Zdroj:	Tetrahedron Letters. 56:3108-3112
ISSN:	0040-4039
DOI:	10.1016/j.tetlet.2014.12.067
Popis:	Bacterial NAD+-dependent DNA ligase (LigA) is an essential enzyme involved in the repair, replication, and recombination of DNA in all bacteria, making it an attractive target in antibacterial drug discovery. A novel series of LigA inhibitors was discovered by combining information from fragment-based lead generation, X-ray crystal structures of previously discovered inhibitors bound to the adenosine binding site of LigA bound to and established structure–activity relationships of LigA inhibitors. The compounds described here were evaluated in a variety of Gram-positive and Gram-negative pathogens as well as evaluation of physical properties.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::4fe2683d6839ef615d9bfebf560d10c8 https://doi.org/10.1016/j.tetlet.2014.12.067 Zobrazit plný text záznamu Full Text from ScienceDirect