VT-NMR analysis clearly showed conformational changes of the tested compounds when the nature of the solvent was changed from polar to apolar. Although some variation was observed between Sanguinamide A and the SA-B peptides, the overall changes seemed to be similar. By determining the structures of the compounds using 2D-NMR experiments, we could confirm conformational changes between polar and apolar environments as well as between Sanguinamide A and the new analogues. Nonetheless, strong differences in exposure of polar groups to the solvent were not observed. One major difference between the new compounds SA-B1 and SA-B3 relative to SA-A1 is the orientation of Ile-6, which is caused by the introduction of the amide which connects it to the backbone aromatic group. The structural change also seems to cause a shift in the backbone by reorienting the aromatic group. Due to this, the directly connected Ala-1 is also shifted and the more distant Phe-2 as well. The other amino acids (Pro-3 -Pro-5) have a rather similar backbone conformation in all molecules and solvents. These relatively minor changes explain how the new analogues SA-B1 and SA-B3 maintain cell permeability, and the reduction in this value is likely caused by the minor conformations that were observed during the NMR measurements for both these compounds (but not for SA-A1).