On the basis of the crystallographically elucidated watersoluble nonameric sequence H-(Tyr-Tyr) 4 -Lys-OH (note: underlined amino acids indicate the D-conformer), the homodimeric dodecamer H-(Phe-Tyr) 5 -Trp-Trp-OH (1) (Fig. 2a, b ) and the covalently linked hairpin species H-(Phe-Tyr) 5 -Trp-Trp-Gly-Lys-Pro-Gly-(Phe-Tyr) 5 Trp-Trp-OH (2) and H-Lys(NBD)-Tyr-(Phe-Tyr) 4 -Trp-Trp-Gly-Lys-([C 2 H 4 O] 2 -CH 2 -CO-gcgtgg-Lys-Lys)-Pro-Gly-(Phe-Tyr) 5 -Trp-Trp-OH (3) (Fig. 2a) (note: gcgtgg represents the nucleobase sequence of aminoethylglycine peptide nucleic acid monomers) were derived via synthetic modification applying solid-phase peptide synthesis (SPPS) and loop design . The transmembrane helices of the latter structures (1-3) are well adapted to the membrane environment as optimized by sequence variation in length and composition (Küsel et al. 2007 ). Through the execution of design studies of the peptide substrates, the preservation of the b 5.6 helical structure ( Fig. 2b ; the superscript denotes the periodicity of the helix), as found for the homodimeric species 1, was maintained for the final hairpin prototype 2 via constant comparison of the respective circular dichroism data resulting from several tested constructs .