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 3H-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-crosslinking studies of ligand receptor interactions.
Hashimoto
M
M
Department of Chemistry, Columbia University, New York, NY 10027, USA.
Liu
Y
Y
Fang
K
K
Li
H Y
HY
Campiani
G
G
Nakanishi
K
K
D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D019921:Biotinylation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D018733:Nicotinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D011073:Polyamines; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014101:Torpedo; D014862:Wasp Venoms / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D018733:Nicotinic Antagonists; D011073:Polyamines; D011978:Receptors, Nicotinic; D014862:Wasp Venoms; C120955:bio-C10-PhTX343-BPP; D001710:Biotin; C034092:delta-philanthotoxin