Synthesis of Interactive Peptide Nanostructures in Living Systems to Control Cellular Function

We explore controlled chemical reactions in complex living systems to generate drug molecules in situ, synthesize interactive peptide nanofibers, or build new cellular compartments. The introduction of bioresponsive groups enables us to control peptide self-assembly inside the living cell. These groups react in a controlled fashion with cellular stimuli, including pH, reactive oxygen species, glutathione, and light. The synthetic intracellular peptide nanostructures can interfere with cell respiration, metabolism, they can induce controlled cell death, or activate T-cells. Additionally, peptide nanostructures can be integrated into the extracellular matrix, where they facilitate nerve regeneration, virus binding to enhance the uptake of viral vectors for gene therapy. To optimize the amphiphilic peptide sequences of self-assembling peptides with regard to their multiscale structure formation and bioactivity, we employ data mining and machine learning tools.

Figure 1. Bioresponsive caged peptide monomers enter living cells and undergo chemical transformations initiated by cellular stimuli and form supramolecular peptide nanofibers that can affect cellular processes.

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