Myelin oligodendrocyte glycoprotein (MOG), a minor myelin component, is an important central nervous system specific target autoantigen for primary demyelination in autoimmune diseases such as multiple sclerosis (MS). The native structure of MOG presents a glycosylation site at position 31 (Asn31). It has been recently described that glycosylation of a MOG peptide epitope improved the detection of specific autoantibodies in sera of MS patients. The solution conformational behavior of two MOG derived peptidesshMOG(30-50) (1) and the glycosylated analogue [Asn31(N-â-Glc)]hMOG(30-50) (2)swere investigated through NMR analysis in a water/HFA solution. Conformational studies revealed that peptides 1 and 2 adopted similar conformations in this environment. In particular, they showed strong propensity to assume a well-defined amphipatic structure encompassing residues 41-48. The N-terminal region resulted to be almost completely unstructured for both peptides. The presence in 1 of a low populated Asx-turn conformation characteristic of the Asn-Xaa-Thr glycosylation sites was the only conformational difference between peptides 1 and 2. Thus, the specific antibody recognition of peptide 2 is most likely driven by direct interactions of the antibody binding site with the Asn-linked sugar moiety.
Conformational Analysis of a Glycosylated Human Oligodendrocyte Glycoprotein Peptide Epitope Able to Detect Antibody Response in Multiple Sclerosis / A. CAROTENUTO; A. D'URSI; E. NARDI; A.M. PAPINI; P. ROVERO. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 44:(2001), pp. 2378-2381. [10.1021/jm010811t]
Conformational Analysis of a Glycosylated Human Oligodendrocyte Glycoprotein Peptide Epitope Able to Detect Antibody Response in Multiple Sclerosis.
PAPINI, ANNA MARIA;ROVERO, PAOLO
2001
Abstract
Myelin oligodendrocyte glycoprotein (MOG), a minor myelin component, is an important central nervous system specific target autoantigen for primary demyelination in autoimmune diseases such as multiple sclerosis (MS). The native structure of MOG presents a glycosylation site at position 31 (Asn31). It has been recently described that glycosylation of a MOG peptide epitope improved the detection of specific autoantibodies in sera of MS patients. The solution conformational behavior of two MOG derived peptidesshMOG(30-50) (1) and the glycosylated analogue [Asn31(N-â-Glc)]hMOG(30-50) (2)swere investigated through NMR analysis in a water/HFA solution. Conformational studies revealed that peptides 1 and 2 adopted similar conformations in this environment. In particular, they showed strong propensity to assume a well-defined amphipatic structure encompassing residues 41-48. The N-terminal region resulted to be almost completely unstructured for both peptides. The presence in 1 of a low populated Asx-turn conformation characteristic of the Asn-Xaa-Thr glycosylation sites was the only conformational difference between peptides 1 and 2. Thus, the specific antibody recognition of peptide 2 is most likely driven by direct interactions of the antibody binding site with the Asn-linked sugar moiety.File | Dimensione | Formato | |
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