Monocyclic β-lactam antibiotics

✍ Scribed by Christopher M. Cimarusti; Richard B. Sykes

• Publisher: John Wiley and Sons
• Year: 1984
• Tongue: English
• Weight: 958 KB
• Volume: 4
• Category: Article
• ISSN: 0198-6325
• DOI: 10.1002/med.2610040103

✦ Synopsis

reevaluation of beta-lactam bond deformation as a criterion for a penicillin-like mode-of-action.

11. MECHANISM OF ACTION

The mechanism of action of the naturally-occurring monobactams was examined at an early They were shown to interact with certain of the penicillin-binding proteins (PBP's) of both gram-positive and gram-negative bacteria, although they showed a lack of affinity for the essential PBP's of these organisms in accord with their poor antibacterial activity. The methoxylated monobactams proved to be good inhibitors of the DD-carboxypeptidase of Streptornyces R61, the model carboxypeptidase used by Ghuysen in his studies of beta-lactams. Methoxylated monobactams, like their penicillin and cephalosporin counterparts, proved to be stable to the action of a wide range of beta-lactamases, bacterial enzymes that hydrolyze the beta-lactam linkage of susceptible beta-lactam antibiotics. Non-methoxylated monobactams, prepared by total synthesis, proved t o be good substrates for these enzymes. This is