Kinetic and thermodynamic properties of MAG antagonists |
| |
Authors: | Stefanie Mesch Hendrik Koliwer-Brandl Oliver Schwardt Beat Ernst |
| |
Affiliation: | a Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstr. 50, 4056 Basel, Switzerland b Center for Biomolecular Interactions Bremen, Glycobiochemistry, University of Bremen, POB 330440, D-28334 Bremen, Germany |
| |
Abstract: | Paraplegia is caused by injuries of the central nervous system (CNS) and especially young people suffer from these severe consequences as, for example, the loss of motor functions. The lack of repair of the injured nerve strands originates from the inhibitory environment for axon regeneration in the CNS. Specific inhibitory proteins block the regrowth of nerve roots. One of these neurite outgrowth inhibitors is the myelin-associated glycoprotein (MAG), which is a member of the Siglec family (sialic acid-binding immunoglobulin-like lectin). In previous studies, we identified potent small molecule MAG antagonists. In this communication, we report new neuraminic acid derivatives modified in the 4- and 5-position, and the influence of various structural modifications on their kinetic and thermodynamic binding properties. |
| |
Keywords: | AIBN, α,α&prime -azodiisobutyronitrile aq, aqueous BnBr, benzyl bromide DCM, dichloromethane DMAP, 4-dimethylaminopyridine DMF, N,N-dimethylformamide FAc, fluoro-acetyl HBS-E, HEPES/NaCl/EDTA buffer HBS-EP, HEPES-NaCl-EDTA-P20 buffer ITC, isothermal titration calorimetry KD, dissociation constant MS, mass spectrometry Neu5Ac, N-acetylneuraminic acid NgR, Nogo receptor NMR, nuclear magnetic resonance PDC, pyridinium dichromate PPTS, pyridinium p-toluenesulfonate RP, reversed phase SPR, surface plasmon resonance STD-NMR, saturation transfer difference nuclear magnetic resonance spectroscopy THF, tetrahydrofuran |
本文献已被 ScienceDirect 等数据库收录! |
|