Kinetic and thermodynamic properties of MAG antagonists

Carbohydr Res. 2010 Jul 2;345(10):1348-59. doi: 10.1016/j.carres.2010.03.010. Epub 2010 Mar 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Discovery
  • Entropy*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Myelin-Associated Glycoprotein / antagonists & inhibitors*
  • Myelin-Associated Glycoprotein / metabolism*
  • Neuraminic Acids / chemistry
  • Neuraminic Acids / metabolism*
  • Neuraminic Acids / pharmacology*
  • Structure-Activity Relationship

Substances

  • Myelin-Associated Glycoprotein
  • Neuraminic Acids