Flexibility, size and hydrophobicity of alkyl side groups in methoxy-poly (ethylene glycol)-polypeptide for the nano-assembly and thermo-sensitivity.

Tailoring of amino acid residues is a feasible strategy to design the structure of peptide for special application. We selected poly(ethylene glycol) and α-amino acids with hydrophobic alkyl side group (L-alanine，L-valine and L-leucine) to synthesize di-block co-polypeptide. The copolymers with methyl side group self-assembled into random coil in majority and aggregated further into stable spherical nanoarchitectures with a little filament owing to the small size, less flexibility and less hydrophobicity of methyl group. By lengthening peptide block, the copolymer self-organized into overwhelming β-sheet and ordered nanorods or nanofibers due to the strengthening hydrophobicity as the copolymers with isopropyl side group did. The copolymers with isobutyl side groups showed cloudy solutions and irregular morphology because the flexibility and large size of isobutyl groups hampered the regular stacking of β-plated sheets and agglomerated into micro-sized precipitates despite of the most hydrophobicity. As temperature rising, both the transition of random coil to β-sheet and PEG dehydration contributed to the sol-gel transition for the copolymers with methyl side group, while PEG dehydration was the primary reason of sol-gel transition for the copolymers with isopropyl side group. In this article, we first disclosed the self-organization process of mPEG-b-polypeptide, which would lay the foundation for the designing of polypeptide-related materials with well-defined properties. How the alkyl side group affects the preliminary secondary structure and the further coordinated self-organized process of the polypeptide materials that we discussed in this paper. Based on the experimental results about secondary structures and morphologies of the comparable copolymers with different side groups, we proposed a three levels of organization process for the copolymers. By this mode of self-organization process, compared to the hydrophobicity, the flexibility or rigid nature of the side group, namely the variation of the side group configuration was more important to determine the stacking regularity of the β-sheet layers and therefore the stability of self-assembled basic nano-structural units and their final size of aggregating entities. [Display omitted] • Less flexible and small methyl group caused random coil. • Flexible and large isobutyl groups hampered the regular stacking of β-sheets. • Appropriate flexibility, size and hydrophobicity of alkyl side groups provoked ordered β-sheet stacking. • Transition of random coil to β-sheet and PEG dehydration induced sol-gel transition. • Ordered stacking of β-sheets stabilized polypeptide against thermal stimulus. [ABSTRACT FROM AUTHOR]