Comparative affinities for penicillin-binding proteins of multipolar ionic amphoteric cephalosporins in gram-negative bacteria.
Chemical modification of the highly reactive 7-aminocephalosporanic acid has yielded many compounds with improved activities and expanded clinical spectra. Introduction of an alpha-oxyimino group in C-7 position has given rise to improved activity against Gram-negative bacteria as a consequence of the high affinity of compounds carrying this substituent for the essential penicillin-binding protein (PBP) 3. The spectrum of activity of oxyimino cephalosporins has been further expanded by introduction of substituents with a quaternary nitrogen in C-3 position. These compounds have maintained their high affinity for the essential PBP 3, typical of the third generation cephalosporins and have acquired an improved ability to cross the outer membranes of Gram-negative bacteria. Among these compounds cefepime also exhibits high affinity for PBP 2, a very unusual property among cephalosporins.
Fontana
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Istituto di Microbiologia, Università degli Studi di Verona, Italy.
Valisena
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Cornaglia
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D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D002511:Cephalosporins / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase