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

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 β peptide, Aβ(16-20) extended at the N terminus with two β-alanine residues. We have studied NH(2)-βAβAKLVFF-COOH (FF), NH(2)-βAβAKLVF-COOH (F), CH(3)CONH-βAβAKLVFF-CONH(2) (CapF), and CH(3)CONH-βAβAKLVFF-CONH(2) (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 β-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 β-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 β-sheet peptides.

Measurement of intrinsic properties of amyloid fibrils by the peak force QNM method

“…Bio Company (USA) and used as received, without further purification and 0.5 wt% solution was prepared by dilution of the peptide in Milli-Q water. 23 26,27 ovalbumin from chicken egg white, bovine serum albumin and insulin were purchased from Sigma. All proteins were dialyzed for one week at 4 C against pH 2 Milli-Q water and freeze-dried.…”

Mechanistic Insight into the Lability of the Benzyloxycarbonyl (Z) Group in N‐Protected Peptides under Mild Basic Conditions

“…Following our previous work on supramolecular hydrogels, 12,13 three isomeric ionizable Z-protected tetrapeptides derived from aspartic acid and phenylalanine were prepared to be used as hydrogelators (Scheme 1). Unexpectedly, we noticed that upon dissolving the peptides in basic water (0.1 M NaOH) the Z groups were rapidly depleted from these molecules at room temperature.…”

Self-Assembled Templates of Aromatic Pentapeptides for Synthesis of CdS Quantum-Dots to Detect the Trace Amounts of Hg²⁺ in Aqueous Solutions

“…Conventional uses of organic dye molecules as fluorescent probes for detection of Hg 2 in aqueous media usually require complicated preparation because of the poor stability of dye molecules in the optical measurement process. This method has low sensitivity and low detection limits, which are subject to be greater restriction for detecting Hg 2 . QDs as fluorescent probes have been used for the detection of Hg 2 ions 9 , and they offer the advantage of greater stability than dye molecules during optical measurements 10,11 .…”

“…S1 Supporting Information, SI . The two chemicals were synthesized by Shanghai Chu PEPTIDE BIOLOGICAL Co., Ltd. 2,3,12 . We found that under specific environments and conditions FFACD aromatic pentapeptides with the N-terminus protected by carboxyl Ac-or a 9-fluorenylmethoxycarbonyl group Fmoc-can act as building blocks that self-assemble to produce nanostructures such as nanotubes, nanobelts, nanofibers, micelles, and vesicles.…”