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.
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