Acetaldehyde, now a big contender: A silyl prolinol derivative was found to catalyze the first Michael addition of acetaldehyde with both aromatic and aliphatic nitroolefins in excellent ...enantioselectivities (see scheme, TMS=trimethylsilyl). The utility of the reaction is illustrated in the synthesis of three current pharmaceuticals and in the synthesis of an enantiopure 3‐monosubstituted pyrrolidine.
Aldehydes react with silyl ethers or the corresponding alcohols and allylsilanes in the presence of catalytic amounts of 2,4‐dinitrobenzenesulfonic acid (DNBA) to provide a wide range of homoallylic ...ethers in moderate to high yields.
Acetaldehyd als Nucleophil in der asymmetrischen Katalyse: Ein Silylprolinol‐Derivat (TMS=Trimethylsilyl) katalysiert die Michael‐Addition von Acetaldehyd mit aromatischen und aliphatischen ...Nitroolefinen in hervorragenden Enantioselektivitäten. Die Reaktion wurde zur Synthese dreier pharmazeutischer Wirkstoffe und eines enantiomerenreinen 3‐substituierten Pyrrolidins angewendet.
N-methyl-d-aspartate receptors (NMDARs) are ion channels whose synaptic versus extrasynaptic localization critically influences their functions. This distribution of NMDARs is highly dependent on ...their lateral diffusion at the cell membrane. Each obligatory subunit of NMDARs (GluN1 and GluN2) contains two extracellular clamshell-like domains with an agonist-binding domain and a distal N-terminal domain (NTD). To date, the roles and dynamics of the NTD of the GluN1 subunit in NMDAR allosteric signaling remain poorly understood. Using single nanoparticle tracking in mouse neurons, we demonstrate that the extracellular neuronal protease tissue-type plasminogen activator (tPA), well known to have a role in the synaptic plasticity and neuronal survival, leads to a selective increase of the surface dynamics and subsequent diffusion of extrasynaptic NMDARs. This process explains the previously reported ability of tPA to promote NMDAR-mediated calcium influx. In parallel, we developed a monoclonal antibody capable of specifically blocking the interaction of tPA with the NTD of the GluN1 subunit of NMDAR. Using this original approach, we demonstrate that the tPA binds the NTD of the GluN1 subunit at a lysine in position 178. Accordingly, when applied to mouse neurons, our selected antibody (named Glunomab) leads to a selective reduction of the tPA-mediated surface dynamics of extrasynaptic NMDARs, subsequent signaling and neurotoxicity, both in vitro and in vivo. Altogether, we demonstrate that the tPA is a ligand of the NTD of the obligatory GluN1 subunit of NMDAR acting as a modulator of their dynamic distribution at the neuronal surface and subsequent signaling.
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