Figure S4.

Differences in permeability of macrocycles with cis-peptide bonds, related to Figure 1

Superposition between the designed structure (blue sticks) and X-ray structure (orange sticks) of three closely related cis-peptide bond-containing designs, D8.13 (left panel), D8.14 (middle panel), and D8.15 (right panel). All three design models match closely (RMSD over all backbone atoms [N, CA, C, O, and CN] < 1.0 Å) with respective X-ray structures. All three design models feature a cis-peptide bond in the validated structures. However, the D8.13 is not permeable in PAMPA, while both D8.14 and D8.15 show significant permeability (P_app > 1 × 10⁻⁷ cm/s), indicating that cis-peptide bond alone is not enough to drive permeability in these macrocycles.