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Molecules 2018, 23(2), 304; https://doi.org/10.3390/molecules23020304

A Cyclic Altered Peptide Analogue Based on Myelin Basic Protein 87–99 Provides Lasting Prophylactic and Therapeutic Protection Against Acute Experimental Autoimmune Encephalomyelitis

1
Laboratory of Molecular Genetics, Hellenic Pasteur Institute, 127 Vasilissis Sophias Ave., 11521 Athens, Greece
2
Department of Chemistry, University of Patras, 26504 Patras, Greece
*
Authors to whom correspondence should be addressed.
Received: 5 December 2017 / Revised: 18 January 2018 / Accepted: 24 January 2018 / Published: 31 January 2018
(This article belongs to the Special Issue Peptide Therapeutics)
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Abstract

In this report, amide-linked cyclic peptide analogues of the 87–99 myelin basic protein (MBP) epitope, a candidate autoantigen in multiple sclerosis (MS), are tested for therapeutic efficacy in experimental autoimmune encephalomyelitis (EAE). Cyclic altered peptide analogues of MBP87–99 with substitutions at positions 91 and/or 96 were tested for protective effects when administered using prophylactic or early therapeutic protocols in MBP72–85-induced EAE in Lewis rats. The Lys91 and Pro96 of MBP87–99 are crucial T-cell receptor (TCR) anchors and participate in the formation of trimolecular complex between the TCR-antigen (peptide)-MHC (major histocompability complex) for the stimulation of encephalitogenic T cells that are necessary for EAE induction and are implicated in MS. The cyclic peptides were synthesized using Solid Phase Peptide Synthesis (SPPS) applied on the 9-fluorenylmethyloxycarboxyl/tert-butyl Fmoc/tBu methodology and combined with the 2-chlorotrityl chloride resin (CLTR-Cl). Cyclo(91–99)[Ala96]MBP87–99, cyclo(87–99)[Ala91,96]MBP87–99 and cyclo(87–99)[Arg91, Ala96]MBP87–99, but not wild-type linear MBP87–99, strongly inhibited MBP72–85-induced EAE in Lewis rats when administered using prophylactic and early therapeutic vaccination protocols. In particular, cyclo(87–99)[Arg91, Ala96]MBP87–99 was highly effective in preventing the onset and development of clinical symptoms and spinal cord pathology and providing lasting protection against EAE induction. View Full-Text
Keywords: myelin basic protein (MBP); experimental autoimmune encephalomyelitis (EAE); multiple sclerosis (MS); altered peptide ligands (APLs); cyclic peptides myelin basic protein (MBP); experimental autoimmune encephalomyelitis (EAE); multiple sclerosis (MS); altered peptide ligands (APLs); cyclic peptides
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Emmanouil, M.; Tseveleki, V.; Triantafyllakou, I.; Nteli, A.; Tselios, T.; Probert, L. A Cyclic Altered Peptide Analogue Based on Myelin Basic Protein 87–99 Provides Lasting Prophylactic and Therapeutic Protection Against Acute Experimental Autoimmune Encephalomyelitis. Molecules 2018, 23, 304.

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