Synthesis of methoxy-X04 derivatives and their evaluation in Alzheimer's disease pathology.
BACKGROUND
Alzheimer's disease is characterized by two notorious protein aggregates in the brain: extracellular senile plaques mainly consisting of amyloid-β peptides and tau-protein-derived intracellular paired helical filaments. The diagnosis of Alzheimer's disease is impaired by insufficient sensitivity and specificity of diagnostic methods to visualize these pathological hallmarks over all disease stages.


OBJECTIVE
The established fluorescence marker methoxy-X04 stains plaques, tau tangles and amyloid-derived angiopathies with good specificity, yet it is limited by slow elimination in vivo. Since the need for new markers is high, we prepared methoxy-X04 derivatives and evaluated their potential as imaging agents in Alzheimer's disease pathology.


RESULTS
In this study, we describe an improved synthesis for methoxy-X04 and its derivatives and their affinity determination for the respective protein targets by immunohistology and a displacement assay.


CONCLUSIONS
This resulted in the identification of new derivatives of methoxy-X04 with improved binding affinity.
Clemens Schöpf-Institute of Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Darmstadt, Germany.
Alexander
A
Boländer
Daniel
D
Kieser
Christoph
C
Scholz
Roland
R
Heyny-von Haußen
Gerhard
G
Mall
Valérie
V
Goetschy
Christian
C
Czech
Boris
B
Schmidt
D000475:Alkenes / Q000138:chemical synthesis*; D000544:Alzheimer Disease / Q000473:pathology*; D001555:Benzene Derivatives / Q000138:chemical synthesis*; D006801:Humans; D013267:Stilbenes
C465418:1,4-bis(4'-hydroxystyryl)-2-methoxybenzene; D000475:Alkenes; D001555:Benzene Derivatives; D013267:Stilbenes