## 1 Introduction  
Multiple sclerosis (MS) is a chronic and inflammatory disease of the central nervous system (CNS) characterized by demyelination and loss of neurologic function [1; 2; 3; 4]. MS is generally considered to be an autoimmune disease in which a coordinated attack of the immune system against components of the myelin sheath occurs [5]. Experimental autoimmune encephalomyelitisitis (EAE), a CD4\({}^{+}\) T cell-mediated disease, is one of the best studied experimental animal models of MS, and represents an invaluable _in vivo_ system for the evaluation of new therapeutic approaches [6; 7]. Candidate autoantigens include constituents of the myelin sheath such as myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). New approaches in applied research for MS include the design and synthesis of peptide analogues of myelin proteins to induce tolerance against the induction of disease [8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18]. MOG is a transmembrane glycoprotein of the CNS and is located on the external surface of the myelin sheath surrounding the neurons. MOG is thought to be one of the autoantigens involved in MS pathology in humans [19; 20; 21; 22; 23]. The main immunodominant region of the MOG protein is the 35-55 epitope, therefore may be a primary target for the stimulation of autoreactive T-cells, in autoimmune diseases of the CNS [24; 25; 26; 27]. The immunodominant epitopes of myelin proteins may be useful for the design and synthesis of mutated peptide analogues (altered peptide ligands, APLs) in the research for the inhibition of EAE.  
The backbone cyclization of peptides has been demonstrated that the _in vivo_ stability is increased and the conformational freedom is reduced. More specifically, cyclic peptides have: (i) greater bioavailability and higher resistance to proteolytic degradation, making them better potential candidates for therapeutic molecules and (ii) more precise conformation and increased receptor selectivity and specificity. The lack of conformational flexibility, which is an important characteristic of linear counterparts, confirms or eliminates their bioactive conformation [28; 29; 30; 31].  
In this work, we pursued, for the first time, the development of an antagonist peptide based on MOG\({}_{35-55}\) epitope and also the development of cyclic peptide analogues and investigated their possible inhibitory effects in the induction of chronic EAE in mice. However, the therapeutic utilization of linear peptides is limited because of their degradation in the presence of proteolytic enzymes [10; 13; 14; 16]. In an effort to develop more stable peptide analogues, without compromising their biological activity, it is necessary to pursue the design of cyclic peptides that are more resistant to proteolytic hydrolysis.  
In this study, we have designed, synthesized and evaluated for their _in vivo_ biological activity in EAE suppression of clinical symptoms, linear and cyclic peptide analogues of MOG\({}_{35-55}\) epitope (based on the human MOG sequence: (MetGluValGlyTrpTyrArg\({}^{41}\)Pro\({}^{42}\)ProPheSerArg\({}^{46}\)ValValHisLeuTyrArg AsnGlyLys) with substitutions in amino acids that interact with the TCR and perhaps play an important role in EAE induction. Human MOG\({}_{35-55}\) epitope differs from rat MOG\({}_{35-55}\) at residue 42, including a Pro instead of Ser. The human MOG\({}_{35-55}\) is weakly encephalitogenic compared to rat MOG\({}_{35-55}\) in C57 BL/6 mice because EAE can be induced by two mechanisms either via an encephalitogenic T cell response to rat MOG\({}_{35-55}\) epitope or by an encephalitogenic B cell response to human MOG\({}_{35-55}\) epitope [32]. The synthesis of linear and cyclic peptides were accomplished on CLTR-Cl resin following the Fmoc/_t_-Bu synthetic methodology.