## 3 Supramolecular Organization of Peptide-Synthetic Polymer Hybrids
PEO-peptidemolecules were postulated to be disposed orthogonally to the fibril axis, which is the contrary to the usual packing of \(\alpha\)-helix homopolopeptides. The observed behavior was rationalized on the basis of the steric repulsion of the second block segment. However, the direct assembly into fibrils could not be fully understood. A related current work based on the control of fibrillation of as \(\beta\)-sheet forming peptide was conducted by [PERSON] _et al._[69]. In this study, a water soluble poly(hydroxyethyl acrylate) [P(HEA)] was conjugated to an azide functionalized \(\beta\)-sheet forming peptide. In terms of supramolecular behavior it was observed that the fibrillation (_i.e._, the \(\beta\)-sheet formation) diminished severely by P(HEA) conjugation. In this case, the polarity and hydrogen bonding of the conjugated polymer appeared to have a major effect on the self-assembly of the hybrid copolymers. Highly polar polymers tended to adopt a random coil conformation as observed by circular dichroism (CD) spectroscopy. The conjugation of P(HEA) to peptides that have a tendency to form aggregates is therefore an interesting potential route towards the control of peptide fibrillation. As it has been previously commented, new packing frustration is introduced by the fact that one or more copolymer blocks are rod-like. In particular, the \(\alpha\)-helical conformation of peptides leads to mesogenic rods which possess dipole moments, potentially include kinks, and have extensively been employed in peptide/polymer hybrid systems [70; 71; 72; 73]. The polymer topology and conformational asymmetry can also influence the final structure. The most recent works exploring both parameters have been conducted by [PERSON] _et al._[74]. Concretely, they focused on the study of ABC miktoarm star repolymers based on an \(\alpha\)-helical mesogenic polypeptide, poly(\(\varepsilon\)-tert-butyloxycarbonyl-L-lysine) (PBLL), and polyisoprene (PI)/polystyrene (PS) as coil-like arms with a wt% composition of the PS, PI, PBLL arms of 30.1, 38.6 and 31.3, respectively. They found that the (PS)(PI)(PBLL) miktoarm formed a hierarchical smectic self-assembly where the \(\alpha\)-helical rod-like PBLL blocks stacked to form independent peptide lamellae while PS and PI blocks constituted lamellae of rectangular cylinders. SAXS measurements led to determine the lamellar periodicity between alternating PBLL and PS/PI lamellae which was of 26 nm. According to the value obtained, their hypothesis was the interdigitation of PBLL \(\alpha\)-helices in an antiparallel manner. This fact was the responsible to control the self-pattern observed by transmission electron and atomic force microscopies. A more recent work, conducted by the same research group, was based on the study of the influence of the side chains of peptide miktoarm star polymers on the solubility, conformation and, therefore, self-assembly in the solid state [75]. These chimeras were constituted by poly(\(\varepsilon\)-tert-butyloxycarbonyl-L-lysine) (PBLL), as the peptide block (A), and polystyrene (PS), as the synthetic segment (B), using A\({}_{2}\)B and A\({}_{2}\)B\({}_{2}\) topologies. It was found that PS\({}_{2}\)PBLL and PS\({}_{2}\)PBLL\({}_{2}\), with protected L-lysine arms, adopted a lamellar block self-assembly showing a better organization (_i.e._, lower steric frustration) for the compound containing four arms (Scheme XI). **Scheme XI. ** Schematic illustration of the packing of the miktoarm molecules in bulk (pink, PS; yellow, polypeptide; blue, surfactant) based on [75]. When the amine groups of poly(L-lysine) were transformed to ammonium acid salts, the supramolecular organization changed from a lamellar self-assembly to micelles in a non-ordered lattice, which was observed by transmission electron microscopy (TEM). By infrared spectroscopy, a number of different amide I bands suggested a mixture of conformations involving \(\alpha\)-helices and \(\beta\)-sheets.