The combination of attractive supramolecular interactions of a hydrophobic Au-metallopeptide with the shielding effect of flexible oligoethylene glycol chains provides access to a stepwise self-assembly of a Au-metalloamphiphile in water. Kinetic control of the supramolecular polymer morphology is achieved using a temperature-dependent assembly protocol, which yields low dispersity supramolecular polymers (metastable state I) or helical bundled nanorods (state II).

The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular therapeutic applications. Protein transduction domains (PTDs) have been used to overcome this barrier, but often require covalent conjugation to their cargo and can be time consuming to synthesize. Synthetic monomers can be designed to mimic the amino acid moieties in PTDs, and their resulting polymers provide a well-controlled platform to vary molecular composition for structure-activity relationship studies. In this paper, a series of polyoxanorbornene-based synthetic mimics, inspired by PTDs, with varying cationic and hydrophobic densities, and the nature of the hydrophobic chain and degree of polymerizations were investigated in vitro to determine their ability to non-covalently transport enhanced green fluorescent protein into HeLa cells, Jurkat T cells, and hTERT mesenchymal stem cells. Polymers with high charge density lead to efficient protein delivery. Similarly, the polymers with the highest hydrophobic content and density proved to be the most efficient at internalization. The observed improvements with increased hydrophobic length and content were consistent across all three cell types, suggesting that these architectural relationships are not cell type specific. However, Jurkat T cells showed distinct variation in uptake between polymers than with the other two cell types. These results provide important design parameters for more effective delivery of biomacromolecules for intracellular delivery applications.

Exploring the role of polymer structure for the internalization of biologically relevant cargo, specifically siRNA, is of critical importance to the development of improved delivery reagents. Herein, we report guanidinium-rich protein transduction domain mimics (PTDMs) based on a ring-opening metathesis polymerization scaffold containing tunable hydrophobic moieties that promote siRNA internalization. Structure-activity relationships using Jurkat T cells and HeLa cells were explored to determine how the length of the hydrophobic block and the hydrophobic side chain compositions of these PTDMs impacted siRNA internalization. To explore the hydrophobic block length, two different series of diblock copolymers were synthesized: one series with symmetric block lengths and one with asymmetric block lengths. At similar cationic block lengths, asymmetric and symmetric PTDMs promoted siRNA internalization in the same percentages of the cell population regardless of the hydrophobic block length; however, with twenty repeat units of cationic charge, the asymmetric block length had greater siRNA internalization, highlighting the non-trivial relationships between hydrophobicity and overall cationic charge. To further probe how the hydrophobic side chains impacted siRNA internalization, an additional series of asymmetric PTDMs was synthesized that featured a fixed hydrophobic block length of five repeat units that contained either dimethyl (dMe), methyl phenyl (MePh), or diphenyl (dPh) side chains and varied cationic block lengths. This series was further expanded to incorporate hydrophobic blocks consisting of diethyl (dEt), diisobutyl (diBu), and dicyclohexyl (dCy) based repeat units to better define the hydrophobic window for which our PTDMs had optimal activity. HPLC retention times quantified the relative hydrophobicities of the non-cationic building blocks. PTDMs containing the MePh, diBu, and dPh hydrophobic blocks were shown to have superior siRNA internalization capabilities compared to their more and less hydrophobic counterparts, demonstrating a critical window of relative hydrophobicity for optimal internalization. This better understanding of how hydrophobicity impacts PTDM-induced internalization efficiencies will help guide the development of future delivery reagents.

The following review gives an overview about synthetic peptide–polymer conjugates as macromolecular building blocks and their self-assembly into a variety of supramolecular architectures, from supramolecular polymer chains, to anisotropic 1D arrays, 2D layers, and more complex 3D networks.

We report the synthesis of ABA' triblock peptide-polysarcosine-peptide conjugates featuring two complementary phenylalanine-histidine pentapeptide strands A/A'. These sequences encode for antiparallel β-sheet formation into folded conjugates, which promote the self-assembly into polysarcosine-shielded core-shell nanorods. These do not cause aggregation of serum proteins in human blood plasma underlining an enhanced stability.

The pH‐responsive nature of two self‐assembled NDI‐peptide amphiphile conjugates is reported. The diethoxy substituted NDI showed a pH‐dependent assembly behaviour, as expected. In contrast, the isopropylamino‐ and ethoxy‐substituted NDI based supramolecular polymer was stable at acidic and basic aqueous conditions. This finding highlights how subtle changes in the molecular design of π‐stacked chromophore‐peptide conjugates have a drastic impact on their equilibrium structure and ultimately functional properties.

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The significance of the dissociation constants obtained for copper sulphate from cryoscopic, spectrophotometric and conductimetric experiments is discussed. New precise spectrophotometric measurements are reported.* University of Reading.f Its significance is blurred in mixed electrolyte solutions.