Advanced

Influence of End-Capping on the Self-Assembly of Model Amyloid Peptide Fragments

Castelletto, Valeria; Hamley, Ian W.; Cenker, Celen LU ; Olsson, Ulf LU ; Adamcik, Jozef; Mezzenga, Raffaele; Miravet, Juan F.; Escuder, Beatriu and Rodriguez-Llansola, Francisco (2011) In The Journal of Physical Chemistry Part B 115(9). p.2107-2116
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of Physical Chemistry Part B
volume
115
issue
9
pages
2107 - 2116
publisher
The American Chemical Society
external identifiers
  • wos:000287833000023
  • scopus:79952274356
ISSN
1520-5207
DOI
10.1021/jp111168s
language
English
LU publication?
yes
id
8a6cf878-6362-4349-ae79-a65f6c379e37 (old id 1869149)
date added to LUP
2011-04-06 12:57:45
date last changed
2017-09-24 03:53:03
@article{8a6cf878-6362-4349-ae79-a65f6c379e37,
  abstract     = {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.},
  author       = {Castelletto, Valeria and Hamley, Ian W. and Cenker, Celen and Olsson, Ulf and Adamcik, Jozef and Mezzenga, Raffaele and Miravet, Juan F. and Escuder, Beatriu and Rodriguez-Llansola, Francisco},
  issn         = {1520-5207},
  language     = {eng},
  number       = {9},
  pages        = {2107--2116},
  publisher    = {The American Chemical Society},
  series       = {The Journal of Physical Chemistry Part B},
  title        = {Influence of End-Capping on the Self-Assembly of Model Amyloid Peptide Fragments},
  url          = {http://dx.doi.org/10.1021/jp111168s},
  volume       = {115},
  year         = {2011},
}