Design of C2-symmetric pseudopeptides for in vivo detection of Cu(ii) through controlled supramolecular nano-assembly

Abstract

Pseudopeptides are emerging next-generation soft bioinspired materials for biological applications. Therefore, a new class of C2-symmetric l-valine-derived pseudopeptides has been designed and developed. The newly developed pseudopeptides exhibit intracellular Cu(ii) ion detection in live-cell fluorescence studies on RAW264.7 cells. We find that the changes in the amino acid side chain in desired pseudopeptidic moieties lead to a drastic change in their selectivity towards different metal ions. The l-valine-derived pseudopeptides exhibit selectivity towards Cu(ii) ions through turn-off fluorescence, and the l-phenylalanine-derived pseudopeptides exhibit selectivity towards Zn(ii) ions through turn-on fluorescence. In addition, the l-valine-derived pseudopeptides show an increase in spherical-shaped structures upon incubation with Cu(ii) ions during supramolecular nano-assembly formation. In contrast, the l-phenylalanine-derived pseudopeptides show a decrease in spherical-shaped structures upon adding Zn(ii) ions. The judiciously designed l-valine-derived and l-phenylalanine-derived bioinspired pseudopeptides are promising for exploring similar effects in various peptidomimetics in advanced biological applications. © 2024 The Royal Society of Chemistry.