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Inhibitors of amyloid fibril formation have been at the centre of intense research efforts for the prevention of amyloidosis. Here, we hypothesise that a specific non-covalent interaction, the thiophilic interaction between the side chain of an aromatic residue in a polypeptide and a sulphur atom of the compound, effectively inhibits amyloid fibril formation. Fluorescence spectroscopy and transmission electron microscopy revealed that sulphur compounds, particularly Cys, inhibit the fibrillisation of amyloid-β 1–40 (Aβ40) and 1–42 (Aβ42). Interestingly, aggregates of Aβ40 and Aβ42 induced by Cys were less cytotoxic than those induced by catechin, which is the most typical inhibitor of amyloid fibril formation. Because the essential amino acid, Cys, is an abundant molecule in the blood and cytosol, our data provide a new basis for the prevention of amyloid-related diseases and the elucidation of the mechanism of these diseases. [ABSTRACT FROM AUTHOR]

Raman optical activity (ROA) has evolved into an incisive probe of structure and conformational transitions in polypeptides and proteins revealing many signal patterns characteristic of specific secondary structural elements. In order to further facilitate analysis of ROA spectral intensity variations, two-dimensional correlation methods are applied to ROA and Raman spectra monitoring the α-helix-to-β-sheet transition in poly(L-lysine) as a function of temperature. Pretreatment of data using background subtraction, normalization and gentle smoothing is essential for the successful generation of 2D ROA correlations, 2D Raman correlations and 2D Raman/ROA heterocorrelations. The pseudoscalar nature of ROA spectra results in detailed 2D correlation analyses providing extensive interpretation of spectral intensity variations. Synchronous plots indicate band assignments consistent with established assignments in poly(L-lysine) together with possible new assignments. Corresponding asynchronous plots probe the temporal sequence of the conformational transition indicating distinct temporal phases while monitoring aggregation through a small amount of β-structure present at the start of the experiment ahead of α-helix unfolding. This study demonstrates the potential of 2D correlation analysis as a valuable technique for the extraction of detailed information about aggregation and conformational transitions in polypeptides and proteins from associated ROA and Raman spectra. Results indicate that aggregation of poly(L-lysine) monomers precedes intramolecular conversion of α-helix to β-sheet, which is then followed by fibril formation. [ABSTRACT FROM AUTHOR]

Presents the table of contents of the volume 32, 2005 issue of the periodical "Journal of Biomolecular NMR."