A Minimalistic Approach to Identify Substrate Binding Features in B1 Metallo?beta?Lactamases

POEYLAUT, A; TOMATIS, P E; KARSISIOTIS, A; DAMBLON, C; MATA, E; VILA, A J

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Elsevier Science Ltd.

Lugar: England; Año: 2007 vol. 17 p. 5171 - 5174

0960-894X

The 2-oxoazetidinylacetate sodium salt was synthesized as a model of a minimal beta-lactam drug. This compound and the monobactam aztreonam were assayed as substrates of the Metallo-beta-lactamase BcII. None of them was hydrolyzed by the enzyme. While the azetidinone was not able to bind BcII, aztreonam was shown to bind in a nonproductive mode. These results provide an explanation for the unability of Metallo-beta-lactamases to inactive monobactams and give some clues for inhibitor design.