Cyclic polypeptide inhibitors

Capreomycin is a mixture of four cyclic polypeptides, of which capreomycin la (R = OH) and lb (R = H) make up 90% of the mixture. Capreomycin is produced by Streptomyces capreolus and is quite similar to the antibiotic viomycin. Little, if anything, is known about its mechanism of action, but if the chemical and pharmacological similarity to viomycin carries over to the mechanism of action, then one might expect something similar. Viomycin is a potent inhibitor of protein synthesis, particularly that which depends on mRNA at the 70S ribosome (53). Viomycin blocks chain elongation by binding to either or both the 50S or 30S ribosomal subunits. A... 

The following polypeptide hormones each interact with receptors in the plasma membrane of their target cells. Which one triggers a signaling pathway that is directly stimulated by treatment of the cell with an inhibitor of cyclic AMP phosphodiesterase ... 

Turning to natural polypeptides and proteins, we may cite our computations on gramicidin S, collagen-like poly (tripeptides), a-lactalbumin, melittin, and bovine pancreatic trypsin inhibitor (BPTI) as examples. In the case of gramicidin S, a cyclic decapeptide, the computed structure [27, 28] was found to agree [29, 30] with a subsequently-determined X-ray structure [31] (see Fig. 2). Likewise, the computed triple-stranded helical structure of poly(Gly-Pro-Pro) [32] (Fig. 3) has cartesian coordinates that agree with those from a single-crystal X-ray diffraction study of (Pro-Pro-Gly)io [33] within 0.3 A. 

Bacitracin, a cyclic peptide, has been shown to block mucopeptide synthesis by inhibiting the dephosphorylation of a lipid pyrophosphate intermediate to lipid phosphate. It prevents the lipid carrier from further participating in the reaction cycle of peptidoglycan synthesis causing accumulation of the lipid pyrophosphate23a,b. The antibiotics enduramycin a (g, basic polypeptide), moenomycin b j d prasinomycin (two phosphorus containing antibiotics) are also inhibitors of mucopeptide synthesis. However, the specific reaction inhibited by these three antibiotics is still not well known. 

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