Synthetic peptides cyclosporin

Synthetic peptides such as oxytocin, vasopressin, ACTH, calcitonin, secretin, somatostatin, cyclosporine, and insulin are already in clinical use. 

An enormous range of medically important polyketide and peptide natural products assembled by modular polyketide synthases (PKSs), non-ribosomal peptide synthases (NRPSs) and mixed PKS/NRPS systems have macrocyclic structures, including the antibiotics erythromycin (PKS) and daptomycin (NRPS), the immunosuppressants cyclosporin (NRPS) and rapamycin (PKS/NRPS), and the antitumor agent epothilone (PKS/NRPS). PKSs and NRPSs are large, multifunctional proteins that are organized into sets of fnnc-tional domains termed modules. The order of modules corresponds directly to the seqnence of monomers in the product. Synthetic intermediates are covalently tethered by thioester linkages to a carrier protein domain in each module. The thiol tether on each carrier domain is phosphopantetheine, which is attached to a conserved serine residne in the carrier protein in a post-translational priming reaction catalyzed by a phosphopantetheinyltransferase. 

Since then, both natural and unnatural cyclic peptides have become important synthetic targets because of their potential applications as antibiotics and other therapeutic agents [50-54]. Selected examples include anticancer agents (ADH-1), antibiotics (colistin), growth hormone inhibitors (octreotide), and immunosuppressant agents (cyclosporine A) (Fig. 6) [55]. 

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