title: Neutral β-Lactams Inactivate High Molecular Mass Penicillin-Binding Proteins of Class B1, Including PBP2a of MRSA.
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 Staphylococcus aureus. 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.
authors.affiliation: Department of Chemistry, Wesleyan University , Middletown, Connecticut 06459, United States.
authors.forename: Kinjal
authors.initials: K
authors.lastname: Dave
authors.affiliation: Departments of Pharmacology, and Biochemistry & Molecular Biology, Baylor College of Medicine , Houston, Texas 77030, United States.
authors.forename: Timothy
authors.initials: T
authors.lastname: Palzkill
authors.affiliation: Department of Chemistry, Wesleyan University , Middletown, Connecticut 06459, United States.
authors.forename: R F
authors.initials: RF
authors.lastname: Pratt
keywords: Penicillin-binding proteins; antibiotics; inhibition; neutral β-lactams