831224-29-4Relevant academic research and scientific papers
From the ganglioside GQ1bα to glycomimetic antagonists of the myelin- associated glycoprotein (MAG)
Ernst, Beat,Schwardt, Oliver,Mesch, Stefanie,Wittwer, Matthias,Rossato, Gianluca,Vedani, Angelo
scheme or table, p. 17 - 22 (2010/09/05)
The tetrasaccharide 4, a substructure of ganglioside GQ1bα, shows a remarkable affinity for the myelinassociated 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 Galβ (1-3)GalNAc, as well as the terminal α (2-3)- and the internal α (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. Schweizerische Chemische Gesellschaft.
