Structure-activity relationship of cyclic thiacarbocyanine tau aggregation inhibitors

Cited 5 time in webofscience Cited 0 time in scopus
  • Hit : 142
  • Download : 3
Macrocyclic bis-thiacarbocyanines are efficacious inhibitors of tau protein aggregation. To extend the structure-activity relationship of this inhibitor class, N,N'-alkylene bis-thiacarbocyanines linked by chains of three to eight methylene carbons were synthesized and examined for inhibitory activity against recombinant human tau aggregation in vitro. At 10 micromolar concentration, inhibitory activity varied with linker length, with four methylene units being most efficacious. On the basis of absorbance spectroscopy measurements, linker length also affected compound folding and aggregation propensity, with a linker length of four methylene units being optimal for preserving open monomer conformation. These data suggest that inhibitory potency can be optimized through control of linker length, and that a contributory mechanism involves modulation of compound folding and aggregation. (C) 2011 Elsevier Ltd. All rights reserved.
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Issue Date
2011-06
Language
English
Article Type
Article
Keywords

FILAMENT FORMATION; POTENT INHIBITION; FIBRILLIZATION; LIGAND; DYE

Citation

BIOORGANIC MEDICINAL CHEMISTRY LETTERS, v.21, no.11, pp.3273 - 3276

ISSN
0960-894X
URI
http://hdl.handle.net/10203/98261
Appears in Collection
CH-Journal Papers(저널논문)
Files in This Item
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 5 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0