Kinetic and thermodynamic properties of MAG antagonists

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.     

New tensio-active molecules stabilize a human G protein-coupled receptor in solution

Structural characterization of membrane proteins is hampered by the instability of the isolated proteins in detergent solutions. Here, we describe a new class of phospholipid-like surfactants that stabilize the G protein-coupled receptor, BLT1. These compounds, called C(13)U(9), C(13)U(19), C(15)U(25) and C(17)U(16), were synthesized by radical polymerization of Tris(hydroxymethyl) acrylamidomethane in the presence of thioglycerol, first endowed with two hydrocarbon chains with variable lengths (13-17 carbon atoms), as transfer reagent. C(13)U(19), C(17)U(16) or C(15)U(25) significantly enhanced the stability of BLT1 in solution compared to what was obtained with common detergents. These molecules therefore represent a promising step towards the structural characterization of BLT1 and possibly other membrane proteins.     

5-Aminosalicylic Acid Protection against Oxidative Damage to Synaptosomal Membranes by Alkoxyl Radicals In Vitro

The antioxidant properties of 5-aminosalicylic acid in vitro were evaluated in a synaptosomal membrane system prepared from gerbil cortical synaptosomes using EPR spin labeling and spectroscopic techniques. MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperidin-1-oxyl) and 5-NS (5-nitroxide stearate) spin labels were used to assess changes in protein oxidation and membrane lipid fluidity, respectively. Synaptosomal membranes were subjected to oxidative stress by incubation with 1 mM azo-bis(isobutyronitrile) (AIBN) or 1 mM 2,2-azobis(amidino propane) dihydrochloride (AAPH) at 37°C for 30 minutes. The EPR analyses of the samples showed significant oxidation of synaptosomal proteins and a decrease in membrane fluidity. 5-Aminosalicylic acid also was evaluated by means of FRAP (the ferric reducing ability of plasma) test as a potential antioxidant. 5-Aminosalicylic acid also showed protection against the oxidation in gerbil cortical synaptosomes system caused by AIBN and AAPH. These results are consistent with the notion of antioxidant protection against free radical induced oxidative stress in synaptosomal membrane system by this agent.