Effect of chirality of small molecule organofluorine inhibitors of amyloid self-assembly on inhibitor potency

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Sood, Abha¹  Abid, Mohammed¹  Hailemichael, Samson¹  Foster, Michelle¹  Toeroek, Bela¹  Toeroek, Marianna¹ 

[1] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA

关键词: Amyloid-beta peptide;    Fibrillogenesis;    Small molecule inhibitor;    Chiral;    Organofluorine;   

DOI  :  10.1016/j.bmcl.2009.10.066

来源: Elsevier

【 摘 要 】

The effect of enantiomeric trifluoromethyl-indolyl-acetic acid ethyl esters on the fibrillogenesis of Alzheimer's amyloid beta (A beta) peptide is described. These compounds have been previously identified as effective inhibitors of the A beta self-assembly in their racemic form. Thioflavin-T Fluorescence Spectroscopy and Atomic Force Microscopy were applied to assess the potency of the chiral target compounds. Both enantiomers showed significant inhibition in the in vitro assays. The potency of the enantiomeric inhibitors appeared to be very similar to each other suggesting the lack of the stereospecific binding interactions between these small molecule inhibitors and the A beta peptide. (C) 2009 Elsevier Ltd. All rights reserved.

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