Structure and property of model peptides of proline/arginine-rich region in bactenecin 5

Bactenecin 5 (Bac 5), a cationic antibacterial peptide, contains a repeating region of Arg-Pro-Pro-X (X = hydrophobic residue). To investigate the structure and property of a Pro/Arg-rich region, we synthesized a series of repeating peptides, Ac-(Arg-Pro-Pro-Phe)n-NHCH3 (n = 2, 4, 6, 8 and 10) (PR2, PR4, PR6, PR8 and PR10,) as models. The circular dichroism (CD) study suggested that the peptides with longer repeats, PR6, PR8 and PR10, formed a conformation similar to poly(proline)-II in aqueous solution. The CD spectra did not change in the presence of dipalmitoyl-d-α-phosphatidylcholine (DPPC), but they changed in the presence of DPPC/dipalmitoyl-dl-3-phosphatidylglycerol (DPPG). The γ-helix, which is very similar in conformation to the poly(proline)-II helix, had the lowest energy conformation for the peptides by energy calculations. Peptides PR6, PR8 and PR10 caused slight leakage of fluorescent dye entrapped in DPPC vesicles, and in the presence of DPPCDPPG, these peptides showed a considerable level of dye-leakage activity. In contrast, the shorter peptides PR2 and PR4 showed no activity. The same tendency was found in measurements of membrane-fusion activity. Judging from these results, the repeating region of Bac 5 may make a framework to hold a conformation resembling the poly(proline)-II structure in aqueous solution. In addition, this region may interact with acidic lipids, resulting in a change in conformation of the peptide. © Munksgaard 1998.