The Effect of PEG Crystallization on the Morphology of PEG/Peptide Block Copolymers Containing Amyloid β‐Peptide Fragments

Abstract

Ordered nanostructures are observed in the melt and solid state for a series of three peptide/PEG conjugates containing fragments of amyloid β‐peptides. These are conjugated to PEG with $\overline M _{\rm n}$ = 3 300 g · mol−1 and a melting temperature Tm = 45–50 °C. The morphology at room temperature is examined by AFM and POM. This shows spherulite formation for the weakly fibrillizing KLVFF‐PEG sample but fibril formation for FFKLVFF‐PEG. The fibrillization tendency of the latter is enhanced by multiple phenylalanine residues. Simultaneous SAXS and WAXS was used to investigate the morphology as a function of temperature. The secondary structure is probed by FTIR.magnified image

Role of Polyalanine Domains in β‐Sheet Formation in Spider Silk Block Copolymers

“…[38][39][40][41] Finally, b-sheet structures found in silks and amyloid proteins also have repetitive motifs. [5,42] Natural occurring silk consists of b-sheet crystalline segments that alternate with amorphous segments. [2] The crystalline segment of B. mori silk is represented by GAGAGS repeat; whereas, N. clavipes spidroin crystalline segment is made of polyalanine or poly(alanylglycine) residues.…”

“…The unit cell dimensions for the crystalline component of the dragline silk of N. clavipes have been found to be a ¼ 0.93 nm, b ¼ 1.04 nm, and c ¼ 0.70 nm, corresponding to a repeat distance of b-sheets, interchain repeat within b-sheets, and intrachain repeat, respectively. [67] Since in the b-strand conformation one amino acid residue contributes 0.35 nm along the molecular chain direction, [42] we expect that the length of one polyalanine block in BA6 peptide will be 4.2 nm. Then the total length of the crystalline segment including all units will be 25.2 nm ( Figure 5).…”

Self assembly of a model amphiphilic phenylalanine peptide/polyethylene glycol block copolymer in aqueous solution

“…We have previously shown that there is a competition between peptide fibrillisation and PEG crystallization in PEG-peptides. In particular, we investigated the series in increasing order of peptide fibrillisation tendency, KLVFF-PEG, AAKLVFF-PEG and FFKLVFF-PEG (all with PEG M n = 3000 g mol − 1 ) [48,49]. In KLVFF-PEG, PEG crystallization strongly disrupted the peptide β-sheet formation, however for FFKLVFF-PEG, PEG crystallization did not occur at the expense of peptide secondary structure formation.…”

Protein-Based Block Copolymers

“…For example, the peptide/protein segment can allow enhanced control over nanoscale structure formation of the synthetic component. The synthetic segment can also reduce toxicity and immunogenicity, and prevent enzymatic degradation or loss of function due to unfolding of the peptide/protein component 48, 49.…”

“…There are diverse routes to prepare hybrid block copolymers 46-48, 50, 51. Controlled radical polymerization, ring opening polymerization, polymerization of macromonomers, and convergent synthesis of peptide-polymer hybrids are some examples.…”