Antibiotic functions

This insertion is accomplished by an enzyme called transpeptidase. -Lactam antibiotics function as substrates for the transpeptidase, thereby establishing selective inhibition of bacterial cell wall synthesis. The structural similarity between -lactam antibiotics and the alanylalanine unit is remarkable as can be seen in Figure 6.8. 

Also on the nucleic acid field, it has been shown95 that the distribution pattern of NH2/NH3 + /OH groups in natural aminoglycosides could indirectly influence their RNA binding properties and therefore their antibiotic functions. Indeed, the number and location of these polar groups is essential to modulate the conformation and dynamics of the glycoside with the concomitant implication for the RNA recognition process. 

Action of /3-lactam antibiotics. /3-Lactam antibiotics function by acylating and inactivating one of the enzymes needed to make the bacterial cell wall. 

A number of antibiotics function by inhibiting transcription. Actinomycin D (see Chap. 16) is an example of one that exerts its effect by binding to the DNA template it can also block DNA replication. 

Since there are some naturally-occurring antibiotics such as the albomycins, which contain the structural features of the siderophores with an appended antibiotic functional unit61,62, synthetic or derivative siderophores may be important new antibiotics 63). In principle these are very effective, since the siderophore antibiotics are recognized as species-generated iron transport agents at the membrane receptor site of producing microorganisms 64). 

Many clinically important antibiotics function by inhibiting protein synthesis. All steps of protein synthesis are susceptible to inhibition by one antibiotic or another. Diphtheria toxin inhibits protein synthesis by covalently modifying an elongation factor, thereby preventing elongation. Ricin, a toxin from castor beans, inhibits elongation by removing a crucial adenine from rRNA. 

Ring I stacks above the base moiety of such that its hydroxyl groups at positions 3 and 4 are directed toward the phosphate moieties of and respectively, but they are not essential for antibiotic function. 

Two reactions that are required to form the precursors of DNA are described in detail ribonucleotide reductase converts ribonucleotides to deoxyribonucleotides, and thymidylate synthase methylates dUMP to form dTMP. The authors present the mechanisms and cofactors of these enzymes and explain how some anticancer drugs and antibiotics function by inhibition of dTMP synthesis and thus the growth of cells. Nucleotides also serve important roles as constituents of NAD", NADP, FAD, and coenzyme A (CoA), so the syntheses of these cofactors are described briefly. The chapter concludes with an explanation of how the purines are catabolized and some of the pathological conditions that arise from defects in the catabolic pathway of the purines. 

Although never commercially marketed, nifurquinazole has been shown to be a powerfixl nitrofuran-based bactericidal. Nitrofuran-based antibiotics function by a complex set of mechanisms that result in the degradation of bacterial macromolecules. Rapid reduction of nitrofurans via flavoproteins, specifically nitrofuran reductase, occurs inside the bacterial cell. The highly reactive species that are generated in this process are ultimately responsible for damage to ribosomal proteins and DNA, and they... 

Some antibiotics function very much like crown ethers. For example, consider the structures of nonactin and monensin. 

It has been hypothesized (Rando, 1975a,b) that the p-lactam antibiotics function as so-called )tcat inhibitors, i.e., they are molecules that become activated only after they interact with a specific target receptor. The hallmark of this hypothesis is that the carboxyl and 6(7)-acylamino side chains serve as handles by which the enzyme can wrench the antibiotic into a geometry with a planar p-lactam nitrogen. The additional strain was supposed to make the p-lactam more reactive. In fact, the molecule s stability would be decreased by such a process, but bonds other than the critical p-lactam C—N bond would be the ones weakened. Also, such a hypothesis is totally inconsistent with the good antibacterial activity of l-carba-2-penems (34) and 2-penems (35) (see Volume 2, Chapters 4 and 5). These molecules have a very pyramidal nitrogen and no... 

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