Synthesis of antagonists of Myelin-associated glycoprotein (MAG) for conformational and SAR studies

Gao, Gan-Pan. Synthesis of antagonists of Myelin-associated glycoprotein (MAG) for conformational and SAR studies. 2004, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_7121

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Damage to the central nervous system (CNS) of higher vertebrates, including humans, often results in
devastating and persistent functional deficits. The limited capacity of the adult mammalian CNS to
repair lesions by axonal regeneration is mainly caused by the inhibitory molecules in myelin: Myelinassociated
glycoprotein (MAG), Nogo, and Oligodendrocyte-myelin glycoprotein (OMgp).
Gangiosides, such as GD1a, GT1b and GQ1bα, are specific functional ligands responsible for MAGmediated
inhibition of neurite outgrowth. Based on the previous SAR studies, partial structure of
natural ligands and derivatives thereof (1, 20, 45, 54α and 54β) were chemically and chemoenzymatically
synthesized. Their biological affinities were tested in a fluorescent hapten inhibition assay; the binding epitopes
were identified by STD NMR; and the bioactive conformations were deduced by trNOEs NMR. This
led to the design of two families of novel mimics with either modifications at the C-9 position of the
α(2,3)-linked terminal sialic acid (87, 97), or substitutions of the disaccharide core by noncarbohydrate
moieties (104-107, 120-122).
Advisors:Ernst, Beat
Committee Members:Schmidt, Richard R. and Hamburger, Matthias Otto
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Ehemalige Einheiten Pharmazie > Molekulare Pharmazie (Ernst)
UniBasel Contributors:Ernst, Beat
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:7121
Thesis status:Complete
Number of Pages:165
Identification Number:
edoc DOI:
Last Modified:22 Jan 2018 15:50
Deposited On:13 Feb 2009 15:05

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