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Article

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

by
Mary Emmanouil
1,
Vivian Tseveleki
1,
Iro Triantafyllakou
2,
Agathi Nteli
2,
Theodore Tselios
2,* and
Lesley Probert
1,*
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.
Molecules 2018, 23(2), 304; https://doi.org/10.3390/molecules23020304
Submission 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.
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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MDPI and ACS Style

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. https://doi.org/10.3390/molecules23020304

AMA Style

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(2):304. https://doi.org/10.3390/molecules23020304

Chicago/Turabian Style

Emmanouil, Mary, Vivian Tseveleki, Iro Triantafyllakou, Agathi Nteli, Theodore Tselios, and Lesley Probert. 2018. "A Cyclic Altered Peptide Analogue Based on Myelin Basic Protein 87–99 Provides Lasting Prophylactic and Therapeutic Protection Against Acute Experimental Autoimmune Encephalomyelitis" Molecules 23, no. 2: 304. https://doi.org/10.3390/molecules23020304

APA Style

Emmanouil, M., Tseveleki, V., Triantafyllakou, I., Nteli, A., Tselios, T., & Probert, L. (2018). A Cyclic Altered Peptide Analogue Based on Myelin Basic Protein 87–99 Provides Lasting Prophylactic and Therapeutic Protection Against Acute Experimental Autoimmune Encephalomyelitis. Molecules, 23(2), 304. https://doi.org/10.3390/molecules23020304

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