0000000000012459
AUTHOR
Patrick Ahlers
Tuneable pH-regulated supramolecular copolymerisation by mixing mismatched dendritic peptide comonomers
Charged phenylalanine-rich dendritic peptides form highly stable and pH-switchable rod-like supramolecular copolymers, when co-assembled with a matching oppositely charged dendritic comonomer. Here, we demonstrate that by mismatching a strong with a weak β-sheet encoded comonomer, both the stability and the pH-triggered disassembly of the copolymers shifts drastically from pH 4.2 to biologically relevant pH 5.8.
Structure and luminescence properties of supramolecular polymers of amphiphilic aromatic thioether–peptide conjugates in water
We present the preparation of luminophore–peptide conjugates that self-assemble into supramolecular polymers in neutral buffer. To this end, we have prepared a small library of six conjugates with varying substitution patterns of the aromatic thioethers, as well as varying amino acid sequences. The latter have allowed us to tune the thermodynamic driving force for self-assembly and probe their photoluminescent properties either in the monomeric or polymeric state, while fully avoiding selective solvent techniques or organic solvent mixtures. All of the supramolecular structures were characterised with transmission electron microscopy, circular dichroism measurements, as well as steady-state…
Dynamic Light Scattering Investigation of the Kinetics and Fidelity of Supramolecular Copolymerizations in Water
The self-assembly of supramolecular copolymers facilitates the preparation of multifunctional materials, with tunable mechanical, electronic, or bioactive properties. Compared to covalent copolymerization protocols, controlling the molecular weight, stability, and monomer sequence of a multicomponent supramolecular copolymer remains limited. Here, we report a light scattering investigation of the charge-regulated supramolecular copolymerization in neutral buffer of physiological ionic strength, supported with electron microscopy and circular dichroism spectroscopy experiments. Dendritic anionic and cationic peptide comonomers self-assemble into AB-type heterocopolymers with a nanorod-like m…
Lipid Bilayer Interactions of Peptidic Supramolecular Polymers and Their Impact on Membrane Permeability and Stability.
The synthesis and physicochemical characterization of supramolecular polymers with tunable assembly profiles offer exciting opportunities, involving the development of new biomedical carriers. Because synthetic nanocarriers aim to transport substances across or toward cellular membranes, we evaluated the interactions of amphiphilic peptide-based supramolecular polymers with lipid bilayers. Here, we focused on nanorod-like supramolecular polymers, obtained from two C3-symmetric dendritic peptide amphiphiles with alternating Phe/His sequences, equipped with a peripheral tetraethylene glycol dendron (C3-PH) or charged ethylenediamine end groups (C3-PH+). Triggered by pH changes, these amphiphi…
Impact of Branching on the Solution Behavior and Serum Stability of Starlike Block Copolymers.
The size control of nanomedicines for tumor diagnosis and therapy is of high importance, since it enables or disables deep and sufficient tumor penetration. Amphiphilic star-shaped block copolypept(o)ides offer substantial promise to precisely adjust the hydrophobic core and the hydrophilic corona, independent of each other, and therefore simultaneously control the size dimension in the interesting size range from 10 to 30 nm. To gain access to core-shell structures of such sizes, 3-arm and 6-arm PeptoStars, based on poly(gamma-tert-butyloxycarbonyl-L-glutamate)-b-polysarcosine (pGlu(OtBu)-b-pSar), were prepared via controlled living ring-opening polymerization (ROP) of the corresponding N-…
Tuning the pH-Switch of Supramolecular Polymer Carriers for siRNA to Physiologically Relevant pH
The preparation of histidine enriched dendritic peptide amphiphiles and their self-assembly into multicomponent pH-switchable supramolecular polymers is reported. Alternating histidine and phenylalanine peptide synthons allow the assembly/disassembly to be adjusted in a physiologically relevant range of pH 5.3-6.0. Coassembly of monomers equipped with dendritic tetraethylene glycol chains with monomers bearing peripheral primary amine groups leads to nanorods with a tunable cationic surface charge density. These surface functional supramolecular polycations are able to reversibly bind short interfering RNA (siRNA). The nanorod-like supramolecular polymers, their complexation with siRNA, and…