We present a new design of peptide–polymer conjugates where a polymer chain is covalently linked to the side chain of a helix bundle-forming peptide. The effect of conjugated polymer chains on the peptide structure was examined using a de novo designed three-helix bundle and a photoactive four-helix bundle. Upon attachment of poly(ethylene glycol) to the exterior of the coiled-coil helix bundle, the peptide secondary structure was stabilized and the tertiary structure, that is, the coiled-coil helix bundle, was retained. When a heme-binding peptide as an example is used, the new peptide–polymer conjugate architecture also preserves the built-in functionalities within the interior of the helix bundle. It is expected that the conjugated polymer chains act to mediate the interactions between the helix bundle and its external environment. Thus, this new peptide–polymer conjugate design strategy may open new avenues to macroscopically assemble the helix bundles and may enable them to function in nonbiological environments.
Amphiphilic peptide-polymer conjugates can lead to hierarchically structured, biomolecular materials. Because the peptide structure determines the size, shape, and intermolecular interactions of these building blocks, systematic understanding of how the peptide structure and functionality are affected upon implementing hydrophobicity is required to direct their assemblies in solution and in the solid state. However, depending on the peptide sequence and native structure, previous studies have shown that the hydrophobic moieties affect peptide structures differently. Here, we present a solution study of amphiphilic peptide-polymer conjugates, where a hydrophobic polymer, polystyrene, is covalently linked to the N-terminus of a coiled-coil helix bundle-forming peptide. The effect of conjugated hydrophobic polymers on the peptide secondary and tertiary structures was examined using two types of model, coiled-coil helix bundles. In particular, the integrity of the binding pocket within the helix bundle upon hydrophobic polymer conjugation was evaluated. Upon attachment of polystyrene to the peptide N-terminus, the coiled-coil helices partially unfolded and functionality within the bundle core was inhibited. These observations are attributed to favorable interactions between hydrophobic residues with the PS block at the peptide-polymer interface that lead to rearrangement of peptide residues and consequently, unfolding of peptide structures. Thus, the hydrophobicity of the covalently linked polymers modifies the conjugates' architecture, size, and shape and may be used to tailor the assembly and disassembly process. Furthermore, the hydrophobicity of the covalently linked polymer needs to be taken into consideration to maintain the built-in functionalities of protein motifs when constructing amphiphilic peptide-polymer conjugates.
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