Treatment of experimental allergic encephalomyelitis (EAE) by a rationally designed cyclic analogue of myelin basic protein (MBP) epitope 72-85.
In this report the rational design, synthesis and pharmacological properties of an amide-linked cyclic antagonist analogue of the guinea pig myelin basic protein epitope MBP(72-85) are described. Design of the potent cyclic analogue was based on 2D NOESY nuclear magnetic resonance and molecular dynamics studies carried out in the linear antagonist Ala81MBP(72-85). The cyclic antagonist completely prevented the induction of experimental allergic/autoimmune encephalomyelitis when coinjected with linear and cyclic agonist analogues MBP(72-85) and cyclo(2-9)MBP(72-85).
Tselios
T
T
Department of Chemistry, University of Patras, Greece.
Daliani
I
I
Deraos
S
S
Thymianou
S
S
Matsoukas
E
E
Troganis
A
A
Gerothanassis
I
I
Mouzaki
A
A
Mavromoustakos
T
T
Probert
L
L
Matsoukas
J
J
D000818:Animals; D015195:Drug Design; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D000939:Epitopes / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D007114:Immunization; D008958:Models, Molecular; D004676:Myelin Basic Protein / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
D000939:Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C118872:myelin basic protein 72-85