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Neutral ?-Lactams Inactivate High Molecular Mass Penicillin-Binding Proteins of Class B1, Including PBP2a of MRSA.

ABSTRACT: The targets of ?-lactam antibiotics are bacterial DD-peptidases (penicillin-binding proteins). ?-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 ?-lactam antibiotics are of comparable activity to the originals against ?-lactam-resistant high molecular mass DD-peptidases of the B1 class, a group that includes PBP2a of methicillin-resistant Staphylococcus aureus. These neutral ?-lactams may direct new development of antibiotics against certain penicillin-resistant bacteria. These molecules do have antibiotic activity against Gram-positive bacteria.

SUBMITTER: Dave K

PROVIDER: S-EPMC4027764 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Neutral β-Lactams Inactivate High Molecular Mass Penicillin-Binding Proteins of Class B1, Including PBP2a of MRSA.

Dave Kinjal K Palzkill Timothy T Pratt R F RF

ACS medicinal chemistry letters 20131216 2

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 Staphyl ...[more]

PMID: 24900789

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