Τμήμα Χημείας

Putative Bioactive Conformations of Amide Linked Cyclic Myelin Basic Protein Peptide Analogues Associated with Experimental Autoimmune Encephalomyelitis

Αγγλικά

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 analysis
has 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 of
the above peptides. Conformational analysis of the three synthetic analogues show that the bioactivity, or
the lack of it, may possibly be due to the distinct local structure observed and the subsequent differences in
the 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-cell
receptor (TCR) on the altered peptide ligand (APL)-MHC complex, whereas more compact structures do
not occlude weak interactions with an approaching TCR and can cause Experimental Autoimmune
Encephalomyelitis (EAE) antagonism. A pharmacophore model based on the structural data has been
generated.

2007

Zinovia, D. Georgios, S. Georgios, E. Mantzourani, T. Mavromoustakos, I. Friligou, T. Theodore

European Journal of Medicinal Chemistry

American Chemical Society (ACS)

50

24

6039-6047

conformation, autoimmune, encephalomyelitis

Θετικές Επιστήμες

https://doi.org/https://doi.org/10.1021/jm070770m

https://doi.org/10.1021/jm070770m

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https://pergamos.lib.uoa.gr/uoa/dl/object/2956640