Self-Assembly of Heterochiral andHomochiral Peptides Conjugated to PNADimers and Their Integration in Peptide-Based Hydrogels

Hybrid biomolecules composed of short peptides and nucleic acid analogues can self-assemble and are good candidates toproduce new materials thanks to their biocompatibility and versatility.
The assembly occurs by exploiting hydrogen bonds and stacking interactions between nucleobases and amino acids. The organization of the molecules at the supramolecular level is dictated by the structure of the assembling units. In this work weexplored the effect of chirality on the self-assembly of PNApeptide conjugates. We focused on homochiral and heterochiral peptides conjugated to PNA dimers and we characterized by spectroscopic techniques the assembled objects. Furthermore, we investigated the ability of the conjugates to form hydrogels in combination with the peptides. The architecture of the assembled molecules in the hydrogels was investigated, as well as the ability of hydrogels to support cell growth. Interestingly, hydrogels formed by homochiral and heterochiral mixtures show pores of different size. In the hydrogels cells grow along a specific direction, dictated by the fiber axis formed by the assembled
compounds and their viability seems related to the gel pore size.

Chem. Eur. J. 2025, 31, e02255 (1 of 10)

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