title: Molecular grafting onto a stable framework yields novel cyclic peptides for the treatment of multiple sclerosis.
abstract: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) and is characterized by the destruction of myelin and axons leading to progressive disability. Peptide epitopes from CNS proteins, such as myelin oligodendrocyte glycoprotein (MOG), possess promising immunoregulatory potential for treating MS; however, their instability and poor bioavailability is a major impediment for their use clinically. To overcome this problem, we used molecular grafting to incorporate peptide sequences from the MOG35-55 epitope onto a cyclotide, which is a macrocyclic peptide scaffold that has been shown to be intrinsically stable. Using this approach, we designed novel cyclic peptides that retained the structure and stability of the parent scaffold. One of the grafted peptides, MOG3, displayed potent ability to prevent disease development in a mouse model of MS. These results demonstrate the potential of bioengineered cyclic peptides for the treatment of MS.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland , Brisbane, QLD 4072, Australia.
authors.forename: Conan K
authors.initials: CK
authors.lastname: Wang
authors.forename: Christian W
authors.initials: CW
authors.lastname: Gruber
authors.forename: Maša
authors.initials: M
authors.lastname: Cemazar
authors.forename: Christopher
authors.initials: C
authors.lastname: Siatskas
authors.forename: Prascilla
authors.initials: P
authors.lastname: Tagore
authors.forename: Natalie
authors.initials: N
authors.lastname: Payne
authors.forename: Guizhi
authors.initials: G
authors.lastname: Sun
authors.forename: Shunhe
authors.initials: S
authors.lastname: Wang
authors.forename: Claude C
authors.initials: CC
authors.lastname: Bernard
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology / Q000517:prevention & control*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D010456:Peptides, Cyclic