title: Synthesis of conjugates of 6-aminophenanthridine and guanabenz, two structurally unrelated prion inhibitors, for the determination of their cellular targets by affinity chromatography.
abstract: The synthesis of affinity matrices for 6-aminophenanthridine (6AP) and 2,6-dichlorobenzylidenaminoguanidine (Guanabenz, GA), two unrelated prion inhibitors, is described. In both cases, the same simple spacer, epsilon-aminocaproylaminopentanol, was introduced by a Mitsunobu reaction and the choice of the anchoring position of the linker was determined by the study of the residual antiprion activity of the corresponding 6AP or GA conjugates. Very recently, these two affinity matrices were used for chromatography assays leading to the identification of ribosome (via the rRNA) as a common target of these two antiprion drugs. Here, we show, using competition experiments with Quinacrine (QC) and Chlorpromazine (CPZ), two other antiprion drugs, that QC, but not CPZ, may also directly target the rRNA.
authors.affiliation: Laboratoire de Chimie Organique 2, INSERM U648, Universite Paris-Descartes, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gug
authors.forename: Nassima
authors.initials: N
authors.lastname: Oumata
authors.forename: Déborah
authors.initials: D
authors.lastname: Tribouillard-Tanvier
authors.forename: Cécile
authors.initials: C
authors.lastname: Voisset
authors.forename: Nathalie
authors.initials: N
authors.lastname: Desban
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bach
authors.forename: Marc
authors.initials: M
authors.lastname: Blondel
authors.forename: Hervé
authors.initials: H
authors.lastname: Galons
mesh_terms: D001667:Binding, Competitive; D002746:Chlorpromazine / Q000378:metabolism; D002846:Chromatography, Affinity; D006143:Guanabenz / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008863:Microspheres; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011328:Prions / Q000037:antagonists & inhibitors*; D011796:Quinacrine / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D012685:Sepharose / Q000737:chemistry
chemical_list: C549408:6-aminophenanthridine; D010617:Phenanthridines; D011328:Prions; D012335:RNA, Ribosomal; D012685:Sepharose; D006143:Guanabenz; D011796:Quinacrine; D002746:Chlorpromazine