Introducing Aliphatic Fluoropeptides: Perspectives on Folding Properties, Membrane Partition and Proteolytic Stability

A de novo designed class of peptide-based fluoropolymers composed of fluorinated aliphatic amino acids as main components is reported. Structural characterization provided insights into fluorine-induced alterations on beta-strand to alpha-helix transition upon an increase in SDS content and revealed the unique formation of PPII structures for trifluorinated fluoropeptides. A combination of circular dichroism, fluorescence-based leaking assays and surface enhanced infrared absorption spectroscopy served to examine the insertion and folding processes into unilamellar vesicles. While partitioning into lipid bilayers, the degree of fluorination conducts a decrease in alpha-helical content. Furthermore, this study comprises a report on the proteolytic stability of peptides exclusively built up by fluorinated amino acids and proved all sequences to be enzymatically degradable despite the degree of fluorination. Herein presented fluoropeptides as well as the distinctive properties of these artificial and polyfluorinated foldamers with enzyme-degradable features will play a crucial role in the future development of fluorinated peptide-based biomaterials.

Automated summary

A new class of peptide-based fluoropolymers composed of fluorinated aliphatic amino acids has been designed. The structural characterization revealed the effects of fluorine-induced alterations and unique formation of PPII structures. Various techniques were employed to examine the insertion and folding processes into lipid vesicles. The degree of fluorination affects the alpha-helical content while partitioning into lipid bilayers. The enzymatic degradability of fluorinated peptides was also studied, showing that all sequences can be degraded despite the degree of fluorination. These fluoropeptides with enzyme-degradable features will be crucial for the future development of fluorinated peptide-based biomaterials.