Honson, Nicolette S., Johnson, Ronald L., Huang, Wenwei,
Inglese, James, Austin, Christopher P., Kuret, Jeff, Differentiating Alzheimer
Disease-Associated Aggregates with Small Molecules, Neurobiology of Disease (2007), doi:
10.1016/j.nbd.2007.07.018

Alzheimer disease is diagnosed postmortem by the density and spatial distribution of β-amyloid
plaques and tau-bearing neurofibrillary tangles. The major protein component of each lesion
adopts cross-β-sheet conformation capable of binding small molecules with submicromolar
affinity. In many cases, however, Alzheimer pathology overlaps with Lewy body disease,
characterized by the accumulation of a third cross-β-sheet forming protein, α-synuclein. To
determine the feasibility of distinguishing tau aggregates from β-amyloid and α-synuclein
aggregates with small molecule probes, a library containing 71,975 small molecules was
screened for antagonists of tau-aggregate mediated changes in Thioflavin S fluorescence,
followed by secondary screens to distinguish the relative affinity for each substrate protein.
Results showed that >10-fold binding selectivity among substrates could be achieved, with
molecules selective for tau aggregates containing at least three aromatic or rigid moieties
connected by two rotatable bonds.

Source & Full text: Genome.gov Neurobiology of Disease

News - TimTec in Publications

MyriaScreen II – diversity screening library from Sigma-Aldrich and TimTec
ApexScreen is a collection of 5,040 compounds that were selected to represent the diversity of TimTec stock
Chemistry reagents, HPLC columns, natural compounds
innovative software packages for chemical database management, chemical web server, structure drawing, diversity analysis, clustering, HTS and combinatorial chemistry, prediction of LogP/solubility/Pk, and Spectra Management