Solution phase synthesis and purification of the minigramicidin ion channels and a succinyl-linked gramicidin

Peptides with alternating d- and l-configured residues as found in the natural ion channel active peptide gramicidin A (gA) are important building blocks for artificially engineered ion channels. We detail an optimised solution phase synthesis employing a convergent assembly of peptide building blocks, giving access to the minigramicidines and a succinyl linked gA derivative on preparative scale. Moreover, the minigramicidines were investigated for secondary structure formation by CD-spectroscopy, which was discovered to be medium and capping-group dependent. A parallel, left-handed double-β-helix seems to be generally favoured in organic solvents for the minigramicidines.