The vast push for bioisosteric replacement of arenes with saturated hydrocarbons has accelerated in recent years. However, the intersection of methodologies for bioisosteric incorporation and the development of peptide therapeutics has been underexplored. Late-stage peptide modifications which exploit saturated hydrocarbons may facilitate syntheses of novel structures and therefore fuel the development of peptide therapeutics. Herein we report the transformation and application of photo-generated thiyl radicals with strain-release of the saturated hydrocarbon [1.1.1] propellane. Harnessing nucelophilic thiyl radicals generated from cysteine residues, we are able to append a bicyclopentane unit onto a number of peptides, using both solution and solid phase synthesis. Additionally, utilizing cystine motifs allows for the direct modification of disulfides, exploiting the “umpolung” reactivity profile of this conventionally electrophilic functionality. This process enables peptide stapling in the absence of a reducing environment, abolishing the need for structural changes before the stapling. These reactions synergistically pair the use of small molecular bioisosteres and late-stage peptide modification to significantly accelerate the discovery of novel peptide therapeutics.