Modulation of the conformational state of the SV2A protein by an allosteric mechanism as evidenced by ligand binding assays.

ABSTRACT:

Background and purpose

Synaptic vesicle protein 2A (SV2A) is the specific binding site of the anti-epileptic drug levetiracetam (LEV) and its higher affinity analogue UCB30889. Moreover, the protein has been well validated as a target for anticonvulsant therapy. Here, we report the identification of UCB1244283 acting as a SV2A positive allosteric modulator of UCB30889.

Experimental approach

UCB1244283 was characterized in vitro using radioligand binding assays with [(3)H]UCB30889 on recombinant SV2A expressed in HEK cells and on rat cortex. In vivo, the compound was tested in sound-sensitive mice.

Key results

Saturation binding experiments in the presence of UCB1244283 demonstrated a fivefold increase in the affinity of [(3)H]UCB30889 for human recombinant SV2A, combi

SUBMITTER: Daniels V 

PROVIDER: S-EPMC3696331 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature