Synthesis of fluorescent probes directed to the active site gorge of acetylcholinesterase.
Six organophosphorus compounds linked to fluorophore groups were prepared in an effort to selectively modify the active site of acetylcholinesterase and deliver probes to the gorge region. Two compounds that vary by the length of a methylene (CH2) group, pyrene-SO2NH(CH2)nNHC(O)CH2CH2P(O)(OEt)(F) (where n = 2 or 3) were found to be potent, irreversible inhibitors of recombinant mouse AChE (Ki approximately 10(5) M(-1) min(-1)). Size exclusion chromatography afforded a fluorescently-labeled cholinesterase conjugate.
Department of Chemistry, The University of Montana, Missoula 59812, USA.
J R
JR
Saltmarsh
A E
AE
Boyd
O P
OP
Rodriguez
Z
Z
Radić
P
P
Taylor
C M
CM
Thompson
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002850:Chromatography, Gel; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D007700:Kinetics; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D005456:Fluorescent Dyes; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; D000110:Acetylcholinesterase