Open AccessCircular dichroism and aggregation studies of amyloid beta (11-8) fragment and its variants.
Author(s) -
Paulina Juszczyk,
Aleksandra S. Kołodziejczyk,
Zbigniew Grzonka
Publication year - 2005
Publication title -
acta biochimica polonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.452
H-Index - 78
eISSN - 1734-154X
pISSN - 0001-527X
DOI - 10.18388/abp.2005_3455
Subject(s) - circular dichroism , fibrillogenesis , chemistry , peptide , amyloid (mycology) , biophysics , protein aggregation , mutant , amyloid beta , helix (gastropod) , fibril , stereochemistry , biochemistry , biology , gene , inorganic chemistry , ecology , snail
Aggregation of Abeta peptides is a seminal event in Alzheimer's disease. Detailed understanding of Abeta assembly would facilitate the targeting and design of fibrillogenesis inhibitors. Here comparative conformational and aggregation studies using CD spectroscopy and thioflavine T fluorescence assay are presented. As a model peptide, the 11-28 fragment of Abeta was used. This model peptide is known to contain the core region responsible for Abeta aggregation. The structural and aggregational behaviour of the peptide was compared with the properties of its variants corresponding to natural, clinically relevant mutants at positions 21-23 (A21G, E22K, E22G, E22Q and D23N). In HFIP (hexafluoro-2-propanol), a strong alpha-helix inducer, the CD spectra revealed an unexpectedly high amount of beta-sheet conformation. The aggregation process of Abeta(11-28) variants provoked by water addition to HFIP was found to be consistent with a model of an alpha-helix-containing intermediate. The aggregation propensity of all Abeta(11-28) variants was also compared and discussed.