Cyclic peptide therapeutics: past, present and future

Abstract

Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics. Over 40 cyclic peptide drugs are currently in clinical use and around one new cyclic peptide drug enters the market every year on average. The vast majority of clinically approved cyclic peptides are derived from natural products, such as antimicrobials or human peptide hormones. New powerful techniques based on rational design and in vitro evolution have enabled the de novo development of cyclic peptide ligands to targets for which nature does not offer solutions. A look at the cyclic peptides currently under clinical evaluation shows that several have been developed using such techniques. This new source for cyclic peptide ligands introduces a freshness to the field, and it is likely that de novo developed cyclic peptides will be in clinical use in the near future.

Post-Translational Tyrosine Geranylation in Cyanobactin Biosynthesis

“…Protein prenylation is thought to improve interactions with membranes, 1-3 while small molecule peptide prenylation 4-6 provides drug-like properties that may improve pharmacological properties such as low membrane permeability and chemical/physical instabilities. 7-10 Among tools to catalyze broad-substrate peptide prenylation, the cyanobactin prenyltransferases are promising. Cyanobactins are ribosomally-synthesized and posttranslationally modified peptide (RiPP) natural products, 11 which are often modified by ABBA prenyltransferases.…”

Improved systemic delivery of insulin by condensed drug loading in a dimpled suppository

“…The novel highly functional peptide therapeutics, such as agents for cancer, diabetes mellitus, cardiovascular diseases, and rheumatoid arthritis, are clinically accessible and were found to have a favorable clinical effect (2)(3)(4). Although these peptides drastically improve the symptoms, their administration method is limited to injections, which lead to patient inconvenience due to pain, risks of infection, and the need for continuous ambulant use.…”

A comparison of pseudoproline substitution effects on cyclisation yield in the total syntheses of segetalins B and G

“…Cyclic peptides and related macrocyclic structures—both natural and synthetic—are of significant interest as novel drug leads, particularly with regards to binding to extended protein surfaces, for example, in the interruption of protein–protein interactions . Numerous cyclic peptides have been isolated from natural sources and these show a wide range of biological activity.…”