Neutral β‑Lactams Inactivate High Molecular
Mass Penicillin-Binding Proteins
of Class B1, Including PBP2a of MRSA
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Abstract
The
targets of β-lactam antibiotics are bacterial DD-peptidases
(penicillin-binding proteins). β-Lactam SAR studies over many
years have demonstrated the importance of a specifically placed negative
charge, usually carboxylate, on these molecules. We show here that
neutral analogues of classical β-lactam antibiotics are of comparable
activity to the originals against β-lactam-resistant high molecular
mass DD-peptidases of the B1 class, a group that includes PBP2a of
methicillin-resistant <i>Staphylococcus aureus</i>. These
neutral β-lactams may direct new development of antibiotics
against certain penicillin-resistant bacteria. These molecules do
have antibiotic activity against Gram-positive bacteria