Self-assembled peptide-based nanocatalysts for bioorthogonal applications

Polymers and nanostructures offer a wide choice of scaffolds to encapsulate and protect bioorthogonal transition metal catalysts (TMCs), enabling the fabrication of stable bioorthogonal nanocatalysts. Amphiphilic polymers are materials with self-assembly properties, capable of encapsulating hydrophobic TMCs to yield bioorthogonal nanocatalysts to operate reactions inside living systems. However, the surfactant nature of these materials interferes with the stability of cellular membranes, restricting the biocompatibility of these structures. This cytotoxicity represents a major constraint that strongly narrows the choice of the possible suitable scaffolds. Small peptide-derivatives are versatile biomolecules with an amphiphilic nature that produce self-assembled structures in aqueous media. Lipopeptides are short aminoacidic sequences bonded to an aliphatic hydrocarbon chain. The difference in polarity between the aminoacidic- (polar) and the hydrophobic- chain (non-polar) results in natural biosurfactants that self-assemble into stable nanoparticles. The peptidic character of the molecules and the soft nature of the formed particles result in a material with broad biocompatibility and minimized cytotoxicity. We hypothesized the possibility of harnessing these molecules to stabilize a hydrophobic metal catalyst in water. We verified this hypothesis by using IKVAV-based lipopeptides to encapsulate a porphyrin-based bioorthogonal TMC, investigating its stability and bioorthogonal catalysis in aqueous media (pro-dye to dye conversion). These peptide derivatives offer an innovative scaffold to prepare nanocatalysts with enhanced biocompatibility, improving the applications of bioorthogonal catalysis in living systems.