Self-Assembling Peptide−Polymer Conjugates Comprising (d-alt-l)-Cyclopeptides as Aggregator Domains

Abstract

The synthesis of peptide−polymer conjugates comprising (d - alt-l)-cyclopeptides as aggregator domains and their self-assembly into tubelike structures is described. By coupling two well-defined poly(n-butyl acrylate) blocks to opposite sides of a preformed cyclic (d - alt-l)-α-octapeptide, a coil−ring−coil bioconjugate was accessed. The applied solution-phase coupling route allowed a multigram scale synthesis of the conjugate and assured both a controlled synthesis and ease of analysis. The controlled self-assembly of the conjugate leads to uniform tube structures. Atomic force microscopy (AFM) of these aggregates deposited on mica revealed a height of 1.4 ± 0.2 nm, a width of 5 nm, and roughly estimated lengths of up to 200−300 nm. A model is proposed, explaining the structure dimensions. This includes the formation of a tubular peptide core build via stacking of the cyclopeptides and a poly(n-butyl acrylate) shell wrapping around the peptide tube. The model is consistent with infrared spectroscopy and electron diffraction measurements, verifying that the peptide segment of the conjugate adopts a β-sheet structure, similar to unsubstituted (d - alt-l)-cyclopeptides. Hence, the stacks of peptide rings are stabilized along the fiber axis via inter-ring β-sheet H-bonding. The tube structures are capable to interact laterally, organizing further into weak networks as was evidenced by AFM and transmission electron microscopy.

Optical properties of amphiphilic copolymer-based self-assemblies

“…After copolymerizing the polymers with hydrophilic coil blocks, in addition to conventional spherical micelles and vesicles, unique self-assembled structures such as helices [53,54], ribbons [55], rings [56], and tubules [57,58] are frequently observed owing to ordered alignment of rigid rods [9]. In the aggregates, the packing style of conjugated rods can remarkably affect the final optical properties.…”

Polymer‐Peptide Block Copolymers – An Overview and Assessment of Synthesis Methods

“…In solution the quantitative coupling of a polymer block to a peptide was achieved with amino acid coupling conditions, albeit the polymer chain was also relatively short ($\overline M _{\rm n}$ = 2 100 g · mol −1 , PDI = 1.10) 75. Interestingly the polymer, carboxylated poly( n ‐butyl acrylate), was coupled not to the N‐terminus of a linear peptide, but to the primary amines of lysine side chains in a cyclic octapeptide.…”

Learning from Nature: β‐Sheet‐Mimicking Copolymers Get Organized

“…[39] Tubelike structures with widths of approximately 4.8 nm that organize further into fiber networks were observed by AFM and TEM. In contrast to Biesalskis work, [35,36] lateral aggregation of the tubes was observed.…”