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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.
AuthorsConan K Wang, Christian W Gruber, Maša Cemazar, Christopher Siatskas, Prascilla Tagore, Natalie Payne, Guizhi Sun, Shunhe Wang, Claude C Bernard, David J Craik
JournalACS chemical biology (ACS Chem Biol) Vol. 9 Issue 1 Pg. 156-63 (Jan 17 2014) ISSN: 1554-8937 [Electronic] United States
PMID24147816 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptides, Cyclic
Topics
  • Amino Acid Sequence
  • Animals
  • Encephalomyelitis, Autoimmune, Experimental (prevention & control)
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Models, Molecular
  • Molecular Sequence Data
  • Multiple Sclerosis (immunology, prevention & control)
  • Myelin-Oligodendrocyte Glycoprotein (chemistry, immunology, therapeutic use)
  • Peptides, Cyclic (chemistry, immunology, therapeutic use)

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