Amphiphilic Peptide−Polymer Conjugates Based on the Coiled-Coil Helix Bundle

Abstract

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.

Responsive hybrid (poly)peptide–polymer conjugates

“…For example, ELPs, 59,84–90 collagen-like peptides (CLPs), 90–93 and helical, alanine-rich peptides, 94,95 have been easily incorporated by our group and others into polymer conjugates. Others have explored the synthesis of amyloidogenic domains, 96,97 coiled-coil sequences, 98,99 and peptides for use as targeting ligands. 100–102 Longer (poly)peptide sequences are produced via recombinant protein expression, providing great control over amino acid sequence for larger polypeptides.…”

“…99, 190–193 Shu et al explored coiled-coil helix bundle forming peptides in which hydrophobic PS was conjugated onto the N-terminus. 99 These conjugates were able to form micelles ca. 10 nm in diameter in the presence of surfactant.…”

“…This study found, in comparison to helical bundles that were conjugated with PEG, that PS denatured the helices and thus cofactor binding was severely limited. 99 Dube et al further explored the effect of various conjugated hydrophobic polymers, PS, PMMA, and PNiPAAM, finding that the peptide structures was greatly affected by the hydrophobicity of the polymer. An intriguing aspect was the use of PNiPAAM, and the ability to disrupt the helicity of the bundle with increasing temperature due to the LCST properties of the polymer.…”

Molecular Modeling of PEGylated Peptides, Dendrimers, and Single-Walled Carbon Nanotubes for Biomedical Applications

“…To increase their solubility and structural stability, coiled coils have been conjugated with PEGs. Experimentally, the Klok group [62][63][64][65][66], the Kros group [67][68][69][70][71], and the Xu group [72][73][74][75][76] synthesized PEGylated coiled coils, characterized their conformation and structure, and investigated the effect of PEGylation on the self-assembled structures and the interactions with other molecules. Computationally, the sequenced-based programs were developed to predict the existence and structure of coiled coils [77][78][79][80][81][82][83], and MD simulations were performed to study the stability of coiled coils [84][85][86][87][88][89][90][91][92][93].…”

Multiple Responsive Polymer-Peptide Bioconjugate

“…(Shu et al 2010) Meanwhile, it's important to get a systematic understanding of how the peptide structure and functionality are affected upon implementing polymer. Peptide-guided selfassembly of synthetic polymers has been proved to be a versatile tool to obtain bio-inspired materials with advanced structural control (Collier and Messersmith 2004;Radu et al 2009).…”