Back to Search
Start Over
From the ganglioside GQ1ba to glycomimetic antagonists of the myelin-associated glycoprotein (MAG)
- Source :
- CHIMIA, Vol 64, Iss 1-2 (2010)
- Publication Year :
- 2010
- Publisher :
- Schweizerische Chemische Gesellschaft, 2010.
-
Abstract
- The tetrasaccharide 4, a substructure of ganglioside GQ1b?, shows a remarkable affinity for the myelin-associated glycoprotein (MAG) and was therefore selected as starting point for a lead optimization program. In our search for structurally simplified and pharmacokinetically improved mimics of 4, antagonists with modifications of the core disaccharide Gal?(1-3)GalNAc, as well as the terminal ?(2-3)- and the internal ?(2-6)-linked neuraminic acid were synthesized and tested in target-based binding assays. Compared to the reference tetrasaccharide 4, the most potent antagonist 17 exhibits a 360-fold improved affinity. Furthermore, pharmacokinetic parameters such as stability in the cerebrospinal fluid, logD and permeation through the BBB indicate the drug-like properties of antagonist 17.
- Subjects :
- Models, Molecular
Mag antagonists
Disaccharide
Oligosaccharides
CHO Cells
Ligands
Docking
chemistry.chemical_compound
Structure-Activity Relationship
Cricetulus
Drug Stability
Glycomimetic
Cricetinae
Gangliosides
Neuraminic acid
Drug Discovery
Tetrasaccharide
Animals
Myelin-associated glycoprotein (mag)
QD1-999
chemistry.chemical_classification
Homology model
Ganglioside
Myelin-associated glycoprotein
Chemistry
Molecular Mimicry
Antagonist
General Medicine
General Chemistry
Hapten inhibition assay
Myelin-Associated Glycoprotein
Biochemistry
Carbohydrate Sequence
Glycoprotein
Protein Binding
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- CHIMIA, Vol 64, Iss 1-2 (2010)
- Accession number :
- edsair.doi.dedup.....b2929de217f8c685d6b50ada2f3c9c52
- Full Text :
- https://doi.org/10.5451/unibas-ep5351