Review: Model peptides and the physicochemical approach to beta-amyloids

beta-Amyloid peptides are the main protein components of neuritic plaques a nd may be important in the pathogenesis of Alzheimer's Disease. The determi nation of the structure of beta-amyloid fibrils poses a challenge because o f the limited solubility of beta-amyloid peptides and the noncrystalline na ture of fibrils formed from these peptides. In this paper, we describe seve ral physicochemical approaches which have been used to examine fibrils and the fibrillogenesis of peptide models of beta-amyloid. Recent advances in s olid state NMR, such as the DRAWS pulse sequence, have made this approach a particularly attractive one for peptides such as beta-amyloid, which are n ot yet amenable to high-resolution solution phase NMR and crystallography. The application of solid state NMR techniques has yielded information on a model peptide comprising residues 10-35 of human beta-amyloid and indicates that in fibrils, this peptide assumes a parallel. beta-strand conformation , with all residues in exact register. In addition, we discuss the use of b lock copolymers of A beta peptides and polyethylene glycol as probes for th e pathways of fibrillogenesis. These methods can be combined with other new methods, such as high-resolution synchrotron X-ray diffraction and small a ngle neutron and X-ray scattering, to yield structural data of relevance no t only to disease, but to the broader question of protein folding and self- assembly. (C) 2000 Academic Press.