Molecular grafting onto a stable framework yields novel cyclic peptides for the treatment of multiple sclerosis

Wang, Conan K., Gruber, Christian W., Cemazar, Masa, Siatskas, Christopher, Tagore, Prascilla, Payne, Natalie, Sun, Guizhi, Wang, Shunhe, Bernard, Claude C. and Craik, David J. (2014) Molecular grafting onto a stable framework yields novel cyclic peptides for the treatment of multiple sclerosis. ACS Chemical Biology, 9 1: 156-163. doi:10.1021/cb400548s


Author Wang, Conan K.
Gruber, Christian W.
Cemazar, Masa
Siatskas, Christopher
Tagore, Prascilla
Payne, Natalie
Sun, Guizhi
Wang, Shunhe
Bernard, Claude C.
Craik, David J.
Title Molecular grafting onto a stable framework yields novel cyclic peptides for the treatment of multiple sclerosis
Journal name ACS Chemical Biology   Check publisher's open access policy
ISSN 1554-8929
1554-8937
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1021/cb400548s
Open Access Status DOI
Volume 9
Issue 1
Start page 156
End page 163
Total pages 8
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID P 24743
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 22 Nov 2013, 20:48:51 EST by Susan Allen on behalf of Institute for Molecular Bioscience