| Abstract
| - The solution models of cyclo(87−99) MBP87-99, cyclo(87−99) [Ala91,96] MBP87-99, and cyclo(87−99) [Arg91,Ala96] MBP87-99 have been determined through 2D NMR spectroscopy in DMSO-d6. Chemical shift analysishas been performed in an attempt to elucidate structural changes occurring upon substitution of native residues.NMR-derived geometrical constraints have been used in order to calculate high-resolution conformers ofthe above peptides. Conformational analysis of the three synthetic analogues show that the bioactivity, orthe lack of it, may possibly be due to the distinct local structure observed and the subsequent differences inthe overall topology and exposed area after binding with Major Histocompatibility Complex II (MHC II).It is believed that an overall larger solvent accessible area blocks the approach and binding of the T-cellreceptor (TCR) on the altered peptide ligand (APL)−MHC complex, whereas more compact structures donot occlude weak interactions with an approaching TCR and can cause Experimental AutoimmuneEncephalomyelitis (EAE) antagonism. A pharmacophore model based on the structural data has beengenerated.
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