Antibiotic structure

Wright GD, Berghuis AM, Mobashery S Aminoglycoside antibiotics. Structures, functions, and resistance. Adv Exp Med Biol 1998,456 27-69. 

Finally, the effect of neomycin-B flexibility on its enzymatic inactivation by Enterococcus faecalis APH(3 ) was tested. This enzyme catalyzes the transfer of a phosphate group from ATP to position 4 of ring I. In this case, the X-ray structure of the enzyme in complex with neomycin-B shows that the antibiotic structure recognized by the enzyme and the target RNA are remarkably similar (see Fig. 7) [40]. In fact, they mainly differ in the conformation adopted by the furanose ring of III (C3-endo and close to C2-endo for the RNA- and enzyme-bound conformations respectively). 

The (3-lactam antibiotics structurally resemble the terminal D-alanyl-D-alanine (o-Ala-o-Ala) in the pen-tapeptides on peptidoglycan (murein) (Fig. 45.1). Bacterial transpeptidases covalently bind the (3-lactam antibiotics at the enzyme active site, and the resultant acyl enzyme molecule is stable and inactive. The intact (3-lactam ring is required for antibiotic action. The (3-lactam ring modifies the active serine site on transpeptidases and blocks further enzyme function. 

Auerbach T, Bashan A, Yonath A. Ribosomal antibiotics structural basis for resistance, synergism and selectivity. Trends Biotechnol. 2004 22 570-576. 

Sandanayaka VP, Prashad AS. Resistance to beta-lactam antibiotics structure and mechanism based design of beta-lactamase inhibitors. Curr Med Chem. 2002 9 1145-1165. 

Other antibiotics structurally analogous to aspergillic acid are... 

Vancomycin is a glycopeptide antibiotic structure, used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. 

Cane DE, Celmer WD, Westley JW. Unified stereochemical model of polyedier antibiotic structure and biogenesis. J. Am. Chem. Soc. 

Tallysomycins A and B, first isolated from fermentation broths of Streptoalloteichus hindustanus, are glycopeptide-derived antitumor antibiotics structurally related to the bleomycins <20010L2811>. 

Hoover JRE. Betalactam antibiotics structure-activity relationships. Demain AL, Solomon NA, editors. Antibiotics Containing the Betalactam-Structure, Part II. Berlin Springer-Verlag, I983 II9. 

Tune BM. Renal tubular transport and nephrotoxicity of p-lactam antibiotics structure-activity relationships. Miner Electrolyte Metab1994 20 221-231. 

Tune BM.The nephrotoxicity of cephalosporin antibiotics-structure-activity relationships. Comm Toxicol 1986 1 (2) 145-170. Goldstein RS, Smith PFTarloff, JB, Contardi L, Rush GF, HookJB. Biochemical mechanisms of cephaloridine nephrotoxicity. Life Sell 988 42(19) 1809-1916. 

Isono, K. Nucleoside antibiotics Structure, biological activity, and biosynthesis. J. Antibiot. (Tokyo) 1988, 41(12), 1711. 

Depsipeptides are near-relatives of peptides, with one or more amide bonds replaced by ester bonds in other words, they are formed by condensing a-amino acids with a-hydroxy-acids in various proportions. There are several important natural examples of these, of defined sequence for example the antibiotic valino-mycin and the family of enniatin antibiotics. Structures of other examples of depsipeptides are given in Section 4.8. 

NMR of Glycopeptide (Vancomycin-Type) Antibiotics Structure and Interaction with... 

After the Second World War, the effort continued to find other novel antibiotic structures. This led to the discovery of the peptide antibiotics (e.g. bacitracin (1945)), chloramphenicol (Fig. 10.72) (1947), the tetracycline antibiotics (e.g. chlortetracycline (Fig. 10.71) (1948)), the macrolide antibiotics (e.g. erythromycin (Fig. 10.73) (1952)), the cyclic peptide antibiotics (e.g. cycloserine (1955)), and in 1955 the first example of a second major group of (3-lactam antibiotics, cephalosporin C (Fig. 10.41). 

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