title: Development of small molecule probes for the beta-amyloid protein of Alzheimer's disease.
abstract: This study describes the synthesis and in vitro testing of small molecule probes that may eventually prove useful as markers of amyloid deposition in living patients. The prototype agent, Chrysamine G (CG), is a derivative of Congo red. CG binds synthetic beta-amyloid well in vitro, as does a fluorinated derivative. The mechanism of binding appears to be the same as Congo red--through a bidentate attachment spanning several amyloid peptide chains. CG is much more lipophilic than Congo red and crosses the blood-brain barrier in normal mice, achieving a brain/blood ratio over 10/1. There was no acute toxicity in mice at doses 10 times those used in the distribution studies. CG appears to be a relatively high affinity probe for beta-amyloid that appears to have low toxicity and can cross the blood-brain barrier. These characteristics are promising for development of in vivo amyloid probes similar to CG.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, PA 15261.
authors.forename: W E
authors.initials: WE
authors.lastname: Klunk
authors.forename: M L
authors.initials: ML
authors.lastname: Debnath
authors.forename: J W
authors.initials: JW
authors.lastname: Pettegrew
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001565:Benzoates; D015415:Biomarkers / Q000032:analysis; D001713:Biphenyl Compounds; D001812:Blood-Brain Barrier; D004396:Coloring Agents / Q000378:metabolism; D005260:Female; D051379:Mice; D015335:Molecular Probes / Q000378:metabolism; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D001565:Benzoates; D015415:Biomarkers; D001713:Biphenyl Compounds; D004396:Coloring Agents; D015335:Molecular Probes; C092559:chrysamine G