Rational design and synthesis of a potent amide-linked cyclic analogue of MBP87-99 based on 2D-NMR studies and molecular dynamics

摘要

We have designed and synthesized altered peptide ligands based on the human myelin basic protein epitope MBP_(87-99) in order to examine whether or not these molecules can treat experimental Allergic Encephalomyelitis (EAE) in Lewis rats.We synthesized an amide-linked cyclic analogue (cyclo(87-99)[Arg~(91),Ala~(96)]MBP_(87-99),by connecting the N-and C-terminus,and a linear analogue [Arg~(91),Ala~(96)]MBP_(87-99) in which Lys~(91) and Pro~(96) were replaced by Arg and Ala,respectively.