Polyglutamine peptides

Several pathological self-polymerizing systems have been biophysi-cally characterized sufficiently to permit identification of protein or peptide species that could serve as molecular targets in a structure-activity relationship. These include transthyretin (TTR) [73-76], serum amyloid A protein (SAA) [77], microtubule-associated protein tau [78-80], amylin or islet amyloid polypeptide (IAPP) [81,82], IgG light chain amyloidosis (AL) [83-85], polyglutamine diseases [9,86], a-synuclein [47,48] and the Alzheimer s (3 peptide [87-96]. A variety of A(3 peptide assay systems have been established at Parke-Davis to search for inhibitors of fibril formation that could be therapeutically useful [97]. 

Altschuler EL, Hud NY, Mazrimas JA, Rupp B. Random coil conformation for extended polyglutamine stretches in aqueous soluble monomeric peptides. J Peptide Res 1997 50 73-75. 

Fig. 9. X-ray intensity distributions (arbitrary scale) from aggregates formed by different polyglutamine peptides (Q , for n = 8,15, 28, 45) polyGln45 (dried), polyGln28 (vapor hydrated), polyGln15 (vapor hydrated), and polyGlng (lyophilized). The vertical bars indicate the positions of the Bragg reflections. The first interference peak for slab stacking of Q8 is indicated by. See Sharma et al. (2005) for further details.

A) Ribbon diagram of an extended polyglutamine sequence forming a cylindrical, parallel /1-helix. The sequence forms a continuous /1-strand, although the peptide whose diffraction served as the basis for the model would only make up one coil. 

Yang W, Dunlap JR, Andrews RB, Wetzel R. Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. Hum Molec Genet 2002 11 2905-17. 

Li Y et al (2007) Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Cell Death Differ 14(12) 2058-2067... 

---