Round and Round we Go: Cyclic Peptides in Disease

Abstract

There is a need for novel drugs for the treatment of infectious diseases, autoimmunity and cancer. Cyclic peptides constitute a class of compounds that have made crucial contributions to the treatment of certain diseases. Penicillin, Vancomycin, Cyclosporin, the Echinocandins and Bleomycin are well-known cyclic peptides. Cyclic peptides, compared to linear peptides, have been considered to have greater potential as therapeutic agents due to their increased chemical and enzymatic stability, receptor selectively, and improved pharmacodynamic properties. They have been used as synthetic immunogens, transmembrane ion channels, antigens for Herpes Simplex Virus, potential immunotherapeutic vaccines for diabetes and Experimental Autoimmune Encephalomyelitis - an animal model of Multiple Sclerosis, as inhibitors against alpha-amylase and as protein stabilizers. Herein, we review important cyclic peptides as therapeutic agents in disease.

Effects of Vaccination with Altered Peptide Ligand on Chronic Pain in Experimental Autoimmune Encephalomyelitis, an Animal Model of Multiple Sclerosis

“…Our study was designed to assess the effects of this mutant peptide on sensory disturbances in EAE animals. In addition, cyclic peptides have been shown to be more stable in vivo , and have similar immunological activity to their linear counterparts (42). For increased stability, the [A 91 ,A 96 ]MBP 87–99 peptide was cyclized from head to tail resulting in cyclo-(87–99)[A 91 ,A 96 ]MBP 87–99 .…”

Phakellistatins: An Underwater Unsolved Puzzle

“…The absence of the free polar C- and N -termini, drastically improves cellular uptake and resistance to enzymatic degradation [12]. Moreover, the reduced flexibility due to macrocyclization, heterocyclization, or cross-linking generally enhances active three-dimensional structures favoring specific binding with proper biological targets [13,14]. Another intriguing feature of cyclic peptides/depsipeptides is represented by the presence of unusual amino acids, such as β-hydroxylated, N -alkylated, d -amino acids, or heterocyclic moieties (oxazolines, oxazoles, thiazolines, and thiazoles, which come from amino acids, such as Ser/Thr and Cys), alternated within standard amino acid sequences.…”

Self-assembled surfactant cyclic peptide nanostructures as stabilizing agents

“…Compared to linear peptides, cyclic peptides have greater potential as stabilizing agents due to their enhanced chemical and enzymatic stability. 13 Microbial cyclic peptide surfactants have been previously reported in the literature. 14,15 Random discovery by screening and challenges in the production of these natural surfactants by synthetic or genetic engineering methods have hindered the further development of these analogs.…”