Tunable Length of Cyclic Peptide–Polymer Conjugate Self-Assemblies in Water

Abstract

Polymers conjugated to cyclic peptides capable of forming strong hydrogen bonds can self-assemble into supramolecular bottlebrushes even in aqueous solutions. However, controlling the aggregation of these supramolecular assemblies remains an obstacle that is yet to be overcome. By introducing pH-responsive poly(dimethylamino ethyl methacrylate) (pDMAEMA) arms, the repulsive forces were tuned by adjusting the degree of protonation on the polymer arms.Neutron scattering experiments demonstrated that conjugates in an uncharged state will self-assemble into supramolecular bottlebrushes. Reducing the pH in the system led to a decrease in the number of aggregation, which was reversible by addition of base. Potentiometric titration showed a correlation between the number of aggregation and the degree of ionization of the pDMAEMA arms. Hence, a balance between the strength of the hydrogen bonds and the repulsive electrostatic interactions determines the number of aggregation and extent of self-assembly. The presented work demonstrates that conjugate selfassociation can be controlled by tuning the charge density on the conjugated polymer arms, paving the way for the use of responsive cyclic peptide conjugates in pharmaceutical applications.

Bisurea-Functionalized RAFT Agent: A Straightforward and Versatile Tool toward the Preparation of Supramolecular Cylindrical Nanostructures in Water

“…[7][8][9] Shortly after, Boué and co-workers designed aromatic bisurea functionalized PEG which self-assemble in a wide range of solvents into long rigid cylinders, which are in dynamic equilibrium with their unimers. 10 Beyond these examples, numerous other supramolecular motifs, such as ureido-pyrimidinone, 12 peptides, [13][14][15] cyclodextrins 16 or benzenetricarboxamide 17,18 have been used to direct the assembly of synthetic water-soluble macromolecules into cylindrical structures. In most of the studies, low molar mass polymers were used, in particular oligo(ethylene glycol)s, and their functionalization by the sticker units was achieved by post-polymerization strategies.…”

Systematic study of the structural parameters affecting the self-assembly of cyclic peptide–poly(ethylene glycol) conjugates

“…Previously, CPs conjugated with polymers, such as poly(2oxazoline)s, poly(2-(diisopropylamino)ethyl methacrylate), 20 poly(dimethylamino ethyl methacrylate), 21 or hydroxyethylacrylamide 13,22 have been studied in this regard, however to date most of the research has focused on the use of poly(ethylene glycol) (PEG). [23][24][25][26] Given this, the present study looks to further our understanding of CP conjugates, by looking at both the Please do not adjust margins Please do not adjust margins grafting density and polymer architecture on the self-assembly process, as well as how the choice of solvent can affect the ultimate length of the nanotube.…”

Peptides with regularly alternating enantiomeric sequence: From ion channel models to bioinspired nanotechnological applications

“…More recently, Perrier's group adopted a click chemistry reaction to couple a cyclic l , d ‐α‐peptide pattern to various responsive polymers. Hybrids with different degrees of functionalization and sensitivity to the environmental stimuli were produced …”

“…The pH‐dependent tubular architectures can also be fabricated by grafting the pH‐sensitive charged polymer poly(dimethylamino ethyl methacrylate) (PDMAEMA) to cyclo [‐( l ‐Trp‐ d ‐Leu‐ l ‐Lys‐ d ‐Leu) 2 ‐] . The self‐assembling properties of the cyclopeptide dramatically change as a function of pH.…”