Amyloid, The Amyloid B -Peptide and Alzheimer’s Disease: Structural Considerations - Molecules: Nucleation, Aggregation and Crystallization - page 289

concentrations (up to 1 mM) and longer analysis time than CD spec-
troscopy does. The high concentrations and the long analysis time result
in an increased risk of polymerization of A β . Therefore, less amyloido-

genic truncated A β -variants or conditions that promote the solubility of

A have often been used in these studies. In the first published study on

full length A

β

40, 40% trifluoroethanol (TFE) in phosphate buffer at pH
2.8 was used (Sticht et al ., 1995). This study showed two helices, Gln15-
Asp23 and Ile31-Met35, with the rest of the peptide being in random-coil
conformation. TFE promotes the formation of ordered secondary struc-
tures, and can thus induce the formation of

β

-sheets. Also
the pH of the solution has a strong influence on secondary structure, and
it is important to study the peptide under physiological conditions. When
A

α -helices or β

40 was studied at pH 5.1 in the presence of sodium dodecylsulfate
(SDS) micelles, which are suggested to mimic the cell membrane to
some extent, the peptide showed an

β

-helical structure from Gln15 to
Val36 interrupted by a kink at Gly25-Asn27. Similar results were
obtained when A

α

42 was studied at pH 7.2 in the presence of SDS
micelles (Shao et al ., 1999). In this study it was concluded that the pep-
tide binds to the surface of the micelles. The presence of an

β

-helix at the
C-terminus of the peptide is in line with the notion that all residues after
Lys28 in A

α

are part of the transmembrane region of APP. By combining
data from NMR-analysis of A

β

40 (using short analysis time to avoid
aggregation, resulting in less detailed data) and A

β

10-35 (which is more
soluble and allows longer analysis times and/or higher concentrations), it
was possible to obtain a structure of A

β

40 in water (Zhang et al ., 2000).
In this case, the peptide showed a compact structure containing loops,
strands and turns, but no

β

-sheets. Later studies in water
confirmed the absence of well-defined secondary structures, but a ten-
dency for the hydrophobic region Leu17-Ala21 to adopt a

α -helices or β

β -strand struc-

ture. Moreover, the two extra residues in A 42, Ile and Ala, resulted in a

more rigid C-terminus with a tendency to form a

β

-strand (Hou et al .,
2004). In summary, both NMR and CD spectroscopy support the notion
that A

β

in a buffer free from detergents and organic solvents is mostly
unstructured.

β