Penicillins, biochemical action

The biochemical basis of penicillin action continues to be an area of active investigation. Penicillins are highly specific inhibitors of enzyme(s) involved in the synthesis of the bacterial cell wall, a structure not present in mammalian cells. Three principal factors are thought to be important for effective antibacterial action by a penicillin ... 

Waxman, D.J. Strominger, J. L. (1983). Penicillin-binding proteins and the mechanism of action of B-lactam antibiotics. Annu. Rev. Biochem. 52, 825-869. 

Penicillin is an antibiotic which destroys bacteria by covalently bonding a transpeptidase enzyme which closes up the cell wall during its biosynthesis. This is its biochemical mechanism of action. See Figure 15. 

After the first successful attempts in 1928 to identify the active biochemicals found in antibacterial molds, followed the rediscovery of penicillin by Fleming, identification of its chemical structure by Hodgkin, and subsequent synthesis by Chain, Heatley, and Florey, which led to the commercial production of penicillin in the mid 1940s [1], Since then, other families of (3-lactam antibiotics have been developed [2, 3], and their massive use worldwide continues to be a forefront line of action against infectious pathogens [4-6]. In recent years, (3-lactams have found other biomedical applications, such as inhibitors of serine protease ([7, 8] for a review, see [9]) and inhibitors of acyl-CoA cholesterol acyltransferasa (ACAT) [10]. Encouraged by their bioactivity, the synthesis and chemistry of (3-lactam antibiotics have been the focus of active research, and chemical modification of some basic structures available from biosynthesis (semisynthetic approaches) as well as the discovery of fully chemical routes to de novo synthesis of (3-lactam... 

From 1935 to 1939 he worked on snake venoms, tumor metabolism, the mechanism of lysozyme action, and the invention and development of methods for biochemical microanalysis. In 1939 he began a systematic study of antibacterial substances produced by microorganisms and the reinvestigation of penicillin. Later he worked on the isolation and elucidation of the chemical structure of penicillin and other natural antibiotics. 

Waxman, D. J.. and Strominger, j. L. 1983. Penicillin binding proteins and the mechanism ot action of p-lactam unlibiolies. Anna Rei>. Biochem. 53 825-869. 

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