Influence of end-capping on the self-assembly of model amyloid peptide fragments

Castelletto, V., Hamley, I. W. ORCID: https://orcid.org/0000-0002-4549-0926, Cenker, C., Olsson, U., Adamcik, J., Mezzenga, R., Miravet, J. F., Escuder, B. and Rodríguez-Llansola, F. (2011) Influence of end-capping on the self-assembly of model amyloid peptide fragments. Journal of Physical Chemistry B, 115 (9). pp. 2107-2116. ISSN 1520-6106 doi: 10.1021/jp111168s

Abstract/Summary

The influence of charge and aromatic stacking interactions on the self-assembly of a series of four model amyloid peptides has been examined. The four model peptides are based on the KLVFF motif from the amyloid Beta peptide, ABeta(16-20) extended at the N terminus with two Beta-alanine residues. We have studied NH2-BetaABetaAKLVFF-COOH (FF), NH2-BetaABetaAKLVFCOOH (F), CH3CONH-BetaABetaAKLVFF-CONH2 (CapF), and CH3CONH-BetaABetaAKLVFFCONH2 (CapFF). The former two are uncapped (net charge plus 2) and differ by one hydrophobic phenylalanine residue; the latter two are the analogous capped peptides (net charge plus 1). The self-assembly characteristics of these peptides are remarkably different and strongly dependent on concentration. NMR shows a shift from carboxylate to carboxylic acid forms upon increasing concentration. Saturation transfer measurements of solvent molecules indicate selective involvement of phenylalanine residues in driving the self-assembly process of CapFF due presumably to the effect of aromatic stacking interactions. FTIR spectroscopy reveals beta-sheet features for the two peptides containing two phenylalanine residues but not the single phenylalanine residue, pointing again to the driving force for self-assembly. Circular dichroism (CD) in dilute solution reveals the polyproline II conformation, except for F which is disordered. We discuss the relationship of this observation to the significant pH shift observed for this peptide when compared the calculated value. Atomic force microscopy and cryogenic-TEM reveals the formation of twisted fibrils for CapFF, as previously also observed for FF. The influence of salt on the self-assembly of the model beta-sheet forming capped peptide CapFF was investigated by FTIR. Cryo-TEM reveals that the extent of twisting decreases with increased salt concentration, leading to the formation of flat ribbon structures. These results highlight the important role of aggregation-induced pKa shifts in the self-assembly of model beta-sheet peptides.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/19360
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Publisher	American Chemical Society
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