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Figure 11.11. Streptogramin A.

antibiotics, such as streptogramin A (Fig. 11.11), virginiamycins M, griseoviridin, are chemically distinct from the B group drugs; they possess a large non-peptide ring with several unsaturated C=C bonds and amide, imide and ester groupings. The A and B components together demonstrate a noticeable synergism of action on bacterial protein synthesis. Like the members of the above-considered B group, the streptogramin A and related antibiotics bind tightly to bacterial ribosomes and specifically to their large (50S) subunits. Again long nascent polypeptides counteract their binding. In accordance with this, puromycin reaction of short donor substrates is inhibited by streptogramin A antibiotics, but peptidyl-puromycin formation on polyribosomes is not. Streptogramin A and viridogrisein were reported to impede both donor- and acceptor-binding sites of PTC of the bacterial ribosome, as well as the binding of aminoacyl-tRNA with A site (presumably in the A/a state). Also the streptogramin A antibiotics prevent the binding of chloramphenicol to ribosomes and 50S ribosomal subunits. At the same time they promote the binding of the B group drugs to bacterial ribosomes. As the synergism, rather than antagonism, between the A and B groups is observed, it is reasonable to assume that their targets are not overlapping and the mechanisms of action are different. It may be that streptogamin A antibiotics block or distort both the a and d sites of PTC in translating ribosomes.

11.5.6.4-Aminohexose

Pyrimidine Nucleoside Antibiotics

This group of antibiotics includes such inhibitors of ribosomal transpeptidation as gougerotin, amicetin, blasticidin S, and bamicetin. The chemical structures of gougerotin and amicetin are given in Fig. 11.12. The antibiotics of this group possess a nucleoside structure and may be regarded as analogs of the tRNA 3'-terminal adenosine. In addition, gougerotin and blasticidin S show the presence of a structural motif traceable in chloramphenicol and lincomycin, e.g. the peptide group with the adjacent Ca-atom. Antibiotics of this group affect bacterial ribosomes although some of them, e.g. gougerotin and blasticidin S, can inhibit eukaryotic ribosomes as well. All these antibiotics bind to the 50S ribosomal subunit and seemingly inhibit the interaction between the acceptor nh2

HOCH2-

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