Treatment of experimental allergic encephalomyelitis (EAE) by a rationally designed cyclic analogue of myelin basic protein (MBP) epitope 72-85

Bioorg Med Chem Lett. 2000 Dec 18;10(24):2713-7. doi: 10.1016/s0960-894x(00)00556-4.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Design*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control
  • Epitopes / administration & dosage
  • Epitopes / pharmacology
  • Guinea Pigs
  • Immunization
  • Models, Molecular
  • Myelin Basic Protein / chemical synthesis
  • Myelin Basic Protein / immunology
  • Myelin Basic Protein / pharmacology*
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology*
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / immunology
  • Peptides, Cyclic / pharmacology
  • Rats
  • Rats, Inbred Lew
  • Spinal Cord / drug effects
  • Spinal Cord / pathology

Substances

  • Epitopes
  • Myelin Basic Protein
  • Peptide Fragments
  • Peptides, Cyclic
  • myelin basic protein 72-85