Preparation and biological properties of biotinylated PhTX derivatives

We report the synthesis of several highly functionalized biotinylated philanthotoxin (PhTX) analogues ( 7 , 8 , 10 , 13 – 16 ) designed on the basis of earlier structure–activity relationship studies. Despite the extensive modifications, the binding to nicotinic acetylcholine receptor (nAChR) is in the low micromolar range according to an inhibition assay using 3 H-thienylcyclohexyl-piperidine (TCP). A patch clamp functional assay gave comparable results. Compounds exemplified by 16 , which consists of a biotinylated ligand linked to a bifunctional photoaffinity probe (BPP), represent a new type of probe which should find use in photo-cross-linking studies of ligand–receptor interactions.