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peptide also undergoes a conformational change at acidic pH from random coil to β-sheetrich amyloid-like fibrils with ribbon-like and tubular morphology [3] (Figure 1).Conformational change and fibril formation of the pure peptides B and C, as well asthe inhibition of amyloid formation in the presence of model peptide A, were studied bycircular dichroism (CD) spectroscopy, time-dependent fluorescence of Thioflavin T (ThT)(Figure 2) or NIAD-4 (Figure 3), transmission-electron microscopy (TEM) and wide-angleX-ray scattering (WAXS), analytical ultracentrifugation (AUC) and size-exclusionchromatography (SEC). The data show a nucleus-dependent growth of amyloid-like fibrilsfor both pure amyloid forming model peptides and a clear inhibition of fibril formation inboth amyloid forming model peptides in the presence of the inhibitor peptide through theformation of soluble α-helical structures in case of peptide B and helical fibers in case ofpeptide C.Fig. 3. (a) NIAD-4 assay of peptide C at pH 4 after different incubation times,(b) in thepresence of one equivalent of A (100µM) and (c) maximum fluorescence intensities as afunction of time (100µM A, 20µM NIAD-4, 10mM acetate buffer, pH 4).Fig. 4. Concept of the inhibitory effect of the ideal coiled coil peptide.These results support the conclusion that the inhibition of amyloid fibril formation inpeptides B and C is due to the formation of heteromeric coiled coil oligomers [4].Evidently, the amyloidogenic target peptide becomes engaged in a stable helicalarrangement when the ideal helical coiled coil peptide A is present during structureformation. Moreover, the ideal coiled coil model peptide is able to disassemble amyloidlikefibrils once they have already formed (data not shown). Hence, the present studiessuggest that stabilization of the helical conformation through the formation of stablecoassemblies could be a promising approach to preventing an amyloidogenic peptide fromconverting into the potentially cytotoxic state.References1. Pagel, K., et al. J. Am. Chem. Soc. 2196-2197 (2006).2. Pagel, K., Koksch, B. Curr. Opin. Chem. Biol. 12, 730-739 (2008).3. Pagel, K., et al. Chem. Eur. J. 11442-11451 (2008).4. Pagel, K., Vagt, T., Koksch, B. Org. Biomol. Chem. 3843-3850 (2005).305