Toward Single-Peak Dalbavancin Analogs through Biology and Chemistry.
ACS Chem Biol
; 14(3): 356-360, 2019 03 15.
Article
em En
| MEDLINE
| ID: mdl-30830742
ABSTRACT
Glycopeptide antibiotics are used to treat severe multidrug resistant infections caused by Gram-positive bacteria. Dalbavancin is a second generation glycopeptide approved for human use, which is obtained from A40926, a lipoglycopeptide produced by Nonomuraea sp. ATCC39727 as a mixture of biologically active congeners mainly differing in the fatty acid chains present on the glucuronic moiety. In this study, we constructed a double mutant of the A40926 producer strain lacking dbv23, and thus defective in mannose acetylation, a feature that increases A40926 production, and lacking the acyltransferases Dbv8, and thus incapable of installing the fatty acid chains. The double mutant afforded the desired deacyl, deacetyl A40926 intermediates, which could be converted by chemical reacylation yielding A40926 analogs with a greatly reduced number of congeners. The newly acylated analogs could then be transformed into dalbavancin analogs possessing the same in vitro properties as the approved drug.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Glicopeptídeos
/
Teicoplanina
/
Antibacterianos
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2019
Tipo de documento:
Article