Cyclic hexapeptides bearing carboxyl groups. Interaction with metal ions and lipid membrane

Three cyclic hexapeptides bearing carboxyl groups, cyclo(L-Asp-L-Phe-L-Pro)2, cyclo(L-Aad-L-Phe-L-Pro)2 (Aad represents alpha-amino adipic acid residue), and cyclo(D-Asp-D-Phe-L-Pro)2 were synthesized and investigated on conformation, complexation with metal ions, and interaction with lipid membrane. These cyclic hexapeptides were found to take several different conformations, though their reference compounds, cyclo(L-Leu-L-Phe-L-Pro)2 and cyclo[D-Asp(OMe)-D-Phe-L-Pro]2, took a single C2 symmetric conformation. Cyclo(D-Asp-D-Phe-L-Pro)2 formed complexes with Ba2+ and Ca2+, whereas cyclo(L-Asp-L-Phe-L-Pro)2 and cyclo(L-Aad-L-Phe-L-Pro)2 did not. The latter two take amphiphilic structures and were distributed to lipid membrane more easily than cyclo(D-Asp-D-Phe-L-Pro)2. Cyclo(D-Asp-L-Phe-L-Pro)2 binds Ca2+ on the lipid membrane.