title: Kinetic and thermodynamic properties of MAG antagonists.
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.
authors.affiliation: Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstr. 50, 4056 Basel, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Mesch
authors.forename: Katrin
authors.initials: K
authors.lastname: Lemme
authors.forename: Hendrik
authors.initials: H
authors.lastname: Koliwer-Brandl
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Strasser
authors.forename: Oliver
authors.initials: O
authors.lastname: Schwardt
authors.forename: Soerge
authors.initials: S
authors.lastname: Kelm
authors.forename: Beat
authors.initials: B
authors.lastname: Ernst
mesh_terms: D055808:Drug Discovery; D019277:Entropy; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D018992:Myelin-Associated Glycoprotein / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009438:Neuraminic Acids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D018992:Myelin-Associated Glycoprotein; D009438:Neuraminic Acids