A minimalistic approach to identify substrate binding features in B1 Metallo-b-lactamases

A.A.POEYLAUT–PALENA, P.E.TOMATIS, A.I.KARSISIOTIS, C.DAMBLON, E.G.MATA AND A.J.VILA

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Elsevier Science Ltd.

Año: 2007 vol. 17 p. 5171 - 5174

0960-894X

    The 2–oxoazetidinylacetate sodium salt was synthesized as a model of a minimal β–lactam drug. This compound and the monobactam aztreonam were assayed as substrates of the Metallo–β–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 non productive mode. These results provide an explanation for the unability of Metallo–β–lactamases to inactive monobactams and give some clues for inhibitor design.