26.11.2012 Views

Peptide-Based Drug Design

Peptide-Based Drug Design

Peptide-Based Drug Design

SHOW MORE
SHOW LESS

Create successful ePaper yourself

Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.

84 Giannakis et al.<br />

(>20 kDa). Laser settings for the higher mass range need to be increased as the<br />

larger molecules require more energy to “fly,” and hence these setting may not be<br />

optimal for detection of smaller peptide fragments and yield off-scale readings.<br />

10. Following the recommendations provided, a R 2 value of >0.95 is easily<br />

obtainable, demonstrating the highly quantitative nature of the technology.<br />

11. The aggregation and lipid-binding assays do not exhibit the same degree of selectivity/specificity<br />

as the Ab capture experiments; hence these assays are useful for<br />

the examination of less complex systems, including synthetic peptides and cell<br />

culture supernatants.<br />

12. During the lipid assay, A� binding time is kept to a minimum to prevent the<br />

peptide further aggregating in the presence of the lipid.<br />

5. Acknowledgments<br />

EG and JDW gratefully acknowledge the Ian Potter Foundation (Australia)<br />

for a grant for the establishment of a biomarker facility at the Howard Florey<br />

Institute. DPS is a Wellcome Trust Travelling Fellow.<br />

References<br />

1. Gorevic, P.D., Goni, F., Pons-Estel, B., Alvarez, F., Peress, N.S. and Frangione, B.<br />

(1986) Isolation and partial characterization of neurofibrillary tangles and amyloid<br />

plaque core in Alzheimer’s disease: immunohistological studies. J. Neuropathol.<br />

Exp. Neurol. 45, 647–664.<br />

2. Masters, C.L., Simms, G., Weinman, N.A., Multhaup, G., McDonald, B.L. and<br />

Beyreuther, K. (1985) Amyloid plaque core protein in Alzheimer disease and Down<br />

syndrome. Proc. Natl. Acad. Sci. USA 82, 4245–4249.<br />

3. Selkoe, D.J. (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol. Rev.<br />

81, 741–766.<br />

4. Sisodia, S.S. and St George-Hyslop, P.H. (2002) Gamma-Secretase, Notch, Abeta<br />

and Alzheimer’s disease: where do the presenilins fit in? Nat. Rev. Neurosci. 3,<br />

281–290.<br />

5. Sisodia, S.S., Koo, E.H., Beyreuther, K., Unterbeck, A. and Price, D.L. (1990)<br />

Evidence that beta-amyloid protein in Alzheimer’s disease is not derived by normal<br />

processing. Science 248, 492–495.<br />

6. Haass, C., Hung, A.Y., Schlossmacher, M.G., Teplow, D.B. and Selkoe, D.J. (1993)<br />

beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms.<br />

J. Biol. Chem. 268, 3021–3024.<br />

7. Jarrett, J.T., Berger, E.P. and Lansbury, Jr. P.T. (1993) The carboxy terminus of the<br />

beta amyloid protein is critical for the seeding of amyloid formation: implications<br />

for the pathogenesis of Alzheimer’s disease. Biochemistry 32, 4693–4697.<br />

8. Lesne, S., Koh, M.T., Kotilinek, L., et al. (2006) A specific amyloid-beta protein<br />

assembly in the brain impairs memory. Nature 440, 352–357.

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!