The donor-acceptor biphenyl platform: a versatile chromophore for the engineering of highly efficient two-photon sensitive photoremovable protecting groups.

Different photoremovable protecting groups in the o-nitrobenzyl, phenacyl, and 2-(o-nitrophenyl)propyl series with a donor-acceptor biphenyl backbone, known to display excellent two-photon absorption cross-sections, were investigated in order to develop efficient two-photon sensitive photoremovable protecting groups. The 2-(o-nitrophenyl)propyl series was a more versatile platform to increase the two-photon sensitivity of photoremovable protecting groups, leading to the p-alkoxy and p-bisalkylamino-4-nitro-[1,1'-biphenyl]-3-yl)propyl derivatives: PENB and EANBP respectively. Those two photoremovable protecting groups are to date the best caging groups for two-photon excitation at 800 and 740 nm respectively, offering attracting perspectives in chemical biology.

α7 nicotinic acetylcholine receptors: a therapeutic target in the structure era.

The nicotinic acetylcholine receptors (nAChR) are ligand-gated ion channels involved in cognitive processes and are associated with brain disorders which makes them interesting drug targets. This article presents a general overview of the receptor to introduce the α7 nAChR as a drug target. The advances in understanding of the structure/function properties of the nAChR produced during the last decade are detailed as they are crucial for rational drug design.

Binding modes of noncompetitive GABA-channel blockers revisited using engineered affinity-labeling reactions combined with new docking studies.

The binding modes of noncompetitive GABA(A)-channel blockers were re-examined taking into account the recent description of the 3D structure of prokaryotic pentameric ligand-gated ion channels, which provided access to new mammalian or insect GABA receptor models, emphasizing their transmembrane portion. Two putative binding modes were deciphered for this class of compounds, including the insecticide fipronil, located nearby either the intra- or the extracellular part of the membrane, respectively. These results are in full agreement with previously described affinity-labeling reactions performed with GABA(A) noncompetitive blockers (Perret et al.

Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors.

GABA(A) receptors are the major inhibitory neurotransmitter receptors in the brain. Some of them are targets of benzodiazepines that are widely used in clinical practice for their sedative/hypnotic, anxiolytic, muscle relaxant and anticonvulsant effects. In order to rationally separate these different drug actions, we need to understand the interaction of such compounds with the benzodiazepine-binding pocket.

Photolabile glutamate protecting group with high one- and two-photon uncaging efficiencies.

A pi-extended [2-(2-nitrophenyl)propoxy]carbonyl (NPPOC) derivative has been prepared as an efficient UV and near-IR photolabile protecting group for glutamate. This glutamate cage compound exhibits efficient photorelease upon one-photon excitation (epsilonPhi=990 M(-1) cm(-1) at 315 nm). In addition, it also shows efficient photorelease in activation of glutamate receptors in electrophysiological recordings.