Screening for inhibitors of tau protein aggregation into Alzheimer paired helical filaments: A ligand based approach results in successful scaffold hopping

Current Alzheimer Research

Volumn 4, Issue 3, 2007, Pages 315-323

  Larbig, Gregor ^a   Pickhardt, Marcus ^b   Lloyd, David G ^c   Schmidt, Boris ^a   Mandelkow, Eckhard ^b  

^a DARMSTADT UNIVERSITY OF TECHNOLOGY   (Germany)

^b MAX PLANCK UNIT FOR STRUCTURAL MOLECULAR BIOLOGY   (Germany)

^c TRINITY COLLEGE DUBLIN   (Ireland)

Author keywords

Alzheimer's disease; Inhibitors; Molecular modeling; Protein aggregation; Tau protein

Indexed keywords

LIGAND; PROTEIN INHIBITOR; TAU PROTEIN; TAU PROTEIN INHIBITOR; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; DRUG SCREENING; HIGH THROUGHPUT SCREENING; IC 50; MOLECULAR MODEL; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN AGGREGATION;

ALZHEIMER DISEASE; ANIMALS; BINDING SITES; DATABASES, FACTUAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HUMANS; HYDRO-LYASES; IMAGING, THREE-DIMENSIONAL; LIGANDS; MODELS, CHEMICAL; NEUROFIBRILLARY TANGLES; TAU PROTEINS;

EID: 34347378629     PISSN: 15672050     EISSN: None     Source Type: Journal    
DOI: 10.2174/156720507781077250     Document Type: Article

References (15)

1. Schmidt B. Aspartic proteases involved in Alzheimer's disease. ChemBioChem 4: 366-378 (2003).
2. De Strooper B, Woodgett J. Alzheimer's disease: Mental plaque removal. Nature 423: 392-393 (2003).
3. Friedhoff P, von Bergen M, Mandelkow EM, Mandelkow E. Structure of tau protein and assembly into paired helical filaments. Biochim Biophys Acta 1502: 122-132 (2000).
4. Pickhardt M, Gazova Z, von Bergen M, Khlistunova I, Wang Y, Hascher A, et al. Anthraquinones inhibit tau aggregation and dissolve Alzheimer's paired helical filaments in vitro and in cells. J Biol Chem 280: 3628-3635 (2005).
5. Böhm HJ, Flohr A, Stahl M. Scaffold hopping. Drug Discovery Today: Technol 1: 217-224 (2004).
6. Renner S, Noeske T, Parsons CG, Schneider P, Weil T, Schneider G. New allosteric modulators of metabotropic glutamate receptor 5 found by ligand-based virtual screening. ChemBioChem 6: 620-625 (2005).
7. Catalyst: Accelrys Inc. Rational Drug Design Scientific Publications: Publications with Catalyst, http://www.accelrys.com/ products/ catalyst/refs.html.
8. Krovat EM, Langer T. Non-peptide angiotensin II receptor antagonists: chemical feature based pharmacophore identification. J Med Chem 46: 716-726 (2003).
9. Hecker EA, Duraiswami C, Andrea TA, Diller DJ. Use of Catalyst pharmacophore models for screening of large combinatorial libraries. J Chem Inf Comp Sci 42: 1204-1211 (2002).
10. Pickhardt M, von Bergen M, Gazova Z, Hascher A, Biernat J, Mandelkow EM, et al. Screening for inhibitors of tau polymerization. Curr Alzheimer Res 2: 219-226 (2005).
11. Catalyst: http://www.accelrys.com/doc/life/catalyst410/tutorials.
12. Biernat J, Gustke N, Drewes G, Mandelkow EM, Mandelkow E. Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding. Neuron 11: 153-163 (1993).
13. Von Bergen M, Friedhoff P, Biernat J, Heberle J, Mandelkow EM, Mandelkow E. Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif (306VQIVYK311) forming β structure. Proc Natl Acad Sci USA 97: 5129-5134 (2000).
14. Friedhoff P, Schneider A, Mandelkow EM, Mandelkow E. Rapid assembly of Alzheimer-like paired helical filaments from microtubule-associated protein tau monitored by fluorescence in solution. Biochemistry 37: 10223-10230 (1998).
15. Schultz TW, Netzeva TI, Roberts DW, Cronin MTD. Structure-toxicity relationships for the effects to tetrahymena pyriformis of aliphatic, carbonyl-containing, α , β-unsaturated chemicals. Chem Res Toxicol 18: 330-341 (2005).