TY - JOUR
T1 - Influence of End-Capping on the Self-Assembly of Model Amyloid Peptide Fragments
AU - Castelletto, Valeria
AU - Hamley, Ian W.
AU - Cenker, Celen
AU - Olsson, Ulf
AU - Adamcik, Jozef
AU - Mezzenga, Raffaele
AU - Miravet, Juan F.
AU - Escuder, Beatriu
AU - Rodriguez-Llansola, Francisco
PY - 2011
Y1 - 2011
N2 - 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, A beta(16-20) extended at the N terminus with two P-alanine residues. We have studied NH2-beta A beta AKLVFF-COOH (FF), NH2-beta A beta AKLVF-COOH (F), CH3CONH-beta A beta AKLVFF-CONH2 (CapF), and CH3CONH-beta A beta AKLVFF-CONH2 (CapFF). The former two are uncapped (net charge +2) and differ by one hydrophobic phenylalanine residue; the latter two are the analogous capped peptides (net charge +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 pK(a) shifts in the self-assembly of model beta-sheet peptides.
AB - 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, A beta(16-20) extended at the N terminus with two P-alanine residues. We have studied NH2-beta A beta AKLVFF-COOH (FF), NH2-beta A beta AKLVF-COOH (F), CH3CONH-beta A beta AKLVFF-CONH2 (CapF), and CH3CONH-beta A beta AKLVFF-CONH2 (CapFF). The former two are uncapped (net charge +2) and differ by one hydrophobic phenylalanine residue; the latter two are the analogous capped peptides (net charge +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 pK(a) shifts in the self-assembly of model beta-sheet peptides.
U2 - 10.1021/jp111168s
DO - 10.1021/jp111168s
M3 - Article
C2 - 21309578
SN - 1520-5207
VL - 115
SP - 2107
EP - 2116
JO - The Journal of Physical Chemistry Part B
JF - The Journal of Physical Chemistry Part B
IS - 9
ER -