Peptidomimetic Wet-Adhesive PEGtides with Synergistic and Multimodal Hydrogen Bonding.

The remarkable underwater adhesion of mussel foot proteins has long been an inspiration in the design of peptidomimetic materials. Although the synergistic wet adhesion of catechol and lysine has been recently highlighted, the critical role of the polymeric backbone has remained largely underexplored. Here, we present a peptidomimetic approach using poly(ethylene glycol) (PEG) as a platform to evaluate the synergistic compositional relation between the key amino acid residues (i.e., DOPA and lysine), as well as the role of the polyether backbone in interfacial adhesive interactions. A series of PEG-based peptides (PEGtides) were synthesized using functional epoxide monomers corresponding to catechol and lysine via anionic ring-opening polymerization. Using a surface force apparatus, highly synergistic surface interactions among these PEGtides with respect to the relative compositional ratio were revealed. Furthermore, the critical role of the catechol-amine synergy and diverse hydrogen bonding within the PEGtides in the superior adhesive interactions was verified by molecular dynamics simulations. Our study sheds light on the design of peptidomimetic polymers with reduced complexity within the framework of a polyether backbone.

Mussel-Inspired Multiloop Polyethers for Antifouling Surfaces.

Despite the widespread use of polymers for antifouling coatings, the effect of the polymeric topology on the antifouling property has been largely underexplored. Unlike conventional brush polymers, a loop conformation often leads to strong steric stabilization of surfaces and antifouling and lubricating behavior owing to the large excluded volume and reduced chain ends. Herein, we present highly antifouling multiloop polyethers functionalized with a mussel-inspired catechol moiety with varying loop dimensions. Specifically, a series of polyethers with varying catechol contents were synthesized via anionic ring-opening polymerization by using triethylene glycol glycidyl ether (TEG) and catechol-acetonide glycidyl ether (CAG) to afford poly(TEG-co-CAG)n. The versatile adsorption and antifouling effects of multiloop polyethers were evaluated using atomic force microscopy and a quartz crystal microbalance with dissipation. Furthermore, the crucial role of the loop dimension in the antifouling properties was analyzed via a surface force apparatus and a cell attachment assay. This study provides a new platform for the development of versatile antifouling polymers with varying topologies.

Mechanochemical Drug Conjugation via pH-Responsive Imine Linkage for Polyether Prodrug Micelles.

Prodrug-type polymer-drug conjugates based on highly biocompatible functional polyethers are developed through mechanochemical post-polymerization modification. Herein, we design functional epoxide monomers of ethoxyethyl glycidyl ether (EEGE) and azidohexyl glycidyl ether (AHGE) and synthesize diblock copolyethers of PEEGE-b-PAHGE via sequential anionic ring-opening polymerization. Subsequent conversion of the functional monomers to the corresponding hydroxyl and amine groups allows for the preparation of double hydrophilic block copolyethers. Most notably, mechanochemical modification allows for the conjugation of these polymers with a highly hydrophobic and potent anticancer agent, cinnamaldehyde, through an imine linkage. The self-assembly of the resulting polymer-drug conjugates into polymeric micelles is characterized by dynamic light scattering and atomic force microscopy. The pH-responsive cleavage of the imine linkages under acidic conditions leads to the release of cinnamaldehyde with a concomitant disassembly of the polymeric micelles. The superior biocompatibility coupled with the solvent-less mechanochemical conjugation approach provides a convenient means to introduce various therapeutics for smart drug delivery.