The oncogenic transcription factor activator protein-1 (AP-1) is a DNA-binding protein that assembles through dimerization of leucine-rich helical sequences of Fos and Jun protein subunits into a coiled-coil. The proto-oncogene cFos (380 residues) was downsized to shorter peptides (37-25 residues) modified with helix-inducing i, i+4 lactam (Lys1-Asp5) constraints to enhance binding to Jun. Structural integrity in the presence and absence of Jun was assessed by circular dichroism spectroscopy, while the thermodynamics of binding was measured by isothermal titration calorimetry. Substitution of the i, i+4 lactams to i, i+4 hydrocarbon staples improved cell permeability, but not to the same magnitude as addition of cationic cell penetrating peptides. Maintaining the helix inducing i, i+4 lactam constraints with the appended cell penetrating peptide, including a nuclear localisation sequence, was the most effective at promoting cell uptake and nuclear localisation.