Title :

Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors

Author(s) :

Flipo, Marion [Auteur]
Biostructures et Decouverte de Medicament
Desroses, Matthieu [Auteur]
Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 [M2SV]
Karolinska Institutet [Stockholm]
Lecat-Guillet, Nathalie [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Villemagne, Baptiste [Auteur]
Biostructures et Decouverte de Medicament
Blondiaux, Nicolas [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Leroux, Florence [Auteur]
Biostructures et Decouverte de Medicament
Piveteau, Catherine [Auteur]
Biostructures et Decouverte de Medicament
Mathys, Vanessa [Auteur]
Molecular Pathology of Tuberculosis [Brussels]
Flament, Marie-Pierre [Auteur]
Siepmann, Juergen [Auteur]
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Villeret, Vincent [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
Wohlkönig, Alexandre [Auteur]
Vlaams Instituut voor Biotechnologie [Ghent, Belgique] [VIB]
Wintjens, René [Auteur]
Université libre de Bruxelles [ULB]
Soror, Sameh [Auteur]
Christophe, Thierry [Auteur]
Institut Pasteur Korea - Institut Pasteur de Corée
Jeon, Hee Kyoung [Auteur]
Institut Pasteur Korea - Institut Pasteur de Corée
Locht, Camille [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Brodin, Priscille [Auteur]
Institut Pasteur Korea - Institut Pasteur de Corée
Déprez, Benoit [Auteur]
Biostructures et Decouverte de Medicament
Baulard, Alain [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Willand, nicolas [Auteur]
Biostructures et Decouverte de Medicament

Journal title :

Journal of Medicinal Chemistry

Pages :

68-83

Publisher :

American Chemical Society

Publication date :

2011-12-06

ISSN :

0022-2623

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Summary In many streptococci, competence for natural DNA transformation is regulated by the Rgg ‐type regulator ComR and the pheromone ComS , which is sensed intracellularly. We compared the ComRS systems of four model ...
Show more >Summary In many streptococci, competence for natural DNA transformation is regulated by the Rgg ‐type regulator ComR and the pheromone ComS , which is sensed intracellularly. We compared the ComRS systems of four model streptococcal species using in vitro and in silico approaches, to determine the mechanism of the ComRS ‐dependent regulation of competence. In all systems investigated, ComR was shown to be the proximal transcriptional activator of the expression of key competence genes. Efficient binding of ComR to DNA is strictly dependent on the presence of the pheromone ( C ‐terminal ComS octapeptide), in contrast with other streptococcal Rgg ‐type regulators. The 20 bp palindromic ComR ‐box is the minimal genetic requirement for binding of ComR , and its sequence directly determines the expression level of genes under its control. Despite the apparent species‐specific specialization of the ComR – ComS interaction, mutagenesis of ComS residues from S treptococcus thermophilus highlighted an unexpected permissiveness with respect to its biological activity. In agreement, heterologous ComS , and even primary sequence‐unrelated, casein‐derived octapeptides, were able to induce competence development in S . thermophilus . The lack of stringency of ComS sequence suggests that competence of a specific S treptococcus species may be modulated by other streptococci or by non‐specific nutritive oligopeptides present in its environment.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL