Research Article
Molecular Grafting onto a Stable Framework Yields Novel Cyclic Peptides for the Treatment of Multiple Sclerosis
Conan
K. Wang, Christian W. Gruber, Maša Cemazar, Christopher Siatskas, Prascilla Tagore, Natalie Payne, Guizhi Sun, Shunhe Wang, Claude C. Bernard, David J. Craik
Published:
October 22, 2013
DOI:
10.1021/cb400548s
License:
Copyright © 2013 American
Chemical Society2013American
Chemical SocietyTerms of Use
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.