Synthesis of conjugates of 6-aminophenanthridine and guanabenz, two structurally unrelated prion inhibitors, for the determination of their cellular targets by affinity chromatography.
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.
Gug
Fabienne
F
Laboratoire de Chimie Organique 2, INSERM U648, Universite Paris-Descartes, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.
Oumata
Nassima
N
Tribouillard-Tanvier
Déborah
D
Voisset
Cécile
C
Desban
Nathalie
N
Bach
Stéphane
S
Blondel
Marc
M
Galons
Hervé
H
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
C549408:6-aminophenanthridine; D010617:Phenanthridines; D011328:Prions; D012335:RNA, Ribosomal; D012685:Sepharose; D006143:Guanabenz; D011796:Quinacrine; D002746:Chlorpromazine