1209013-07-9Relevant academic research and scientific papers
Low molecular weight antagonists of the myelin-associated glycoprotein: Synthesis, docking, and biological evaluation
Mesch, Stefanie,Moser, Delia,Strasser, Daniel S.,Kelm, Antje,Cutting, Brian,Rossato, Gianluca,Vedani, Angelo,Koliwer-Brandl, Hendrik,Wittwer, Matthias,Rabbani, Said,Schwardt, Oliver,Kelm, Soerge,Ernst, Beat
experimental part, p. 1597 - 1615 (2010/08/05)
The injured adult mammalian central nervous system is an inhibitory environment, for axon regeneration due to specific inhibitors, among them themyelin-associated glycoprotein (MAG), a member of the Siglec family (sialic-acid binding immunoglobulin-like lectin). In earlier studies, we identified the lead structure 5, which shows a 250-fold improved in vitro affinity for MAG compared to the tetrasaccharide binding epitope of GQ1bα (1), the best physiological MAG ligand described so far. By modifying the 2- and 5-position, the affinity of 5 could be further improved to the nanomolar range (→19a). Docking studies to a homology model of MAG allowed the rationalization of the experimental binding properties. Finally, pharmacokinetic parameters (stability in the cerebrospinal fluid, logD and permeation through the BBB) indicate the drug-like properties of the high-affinity antagonist 19a.
