Rational design of peptide nanotubes for varying diameters and lengths

Amphiphilic helical peptides (Sar)(m)-b-(L-Leu-Aib)(n) (m = 22-25; n = 7, 8, 10) with a hydrophobic block as a right-handed helix were synthesized and their mixtures with (Sar)(25)-b-(D-Leu-Aib)(6) containing the hydrophobic block as a left-handed helix were examined in their molecular assembly formation. The single component (Sar)(25)-b-(D-Leu-Aib)(6) forms peptide nanotubes of 70 nm diameter and 200 nm length. The two-component mixtures of (Sar)(25)-b-(D-Leu-Aib)(6) with (Sar)(24)-b-(L-Leu-Aib)(7), (Sar)(22)-b-(L-Leu-Aib)(8), and (Sar)(25)-b-(L-Leu-Aib)(1)0 yield peptide nanotubes of varying dimensions with 200 nm diameter and 400 nm length, 70 nm diameter and several micrometer length (maximum 30 mu m), and 70 nm diameter and 100-600 nm length, respectively. The right-handed and the left-handed helix were thus found to be molecularly mixed due to the stereo-complex formation and to generate nanotubes of different sizes. When the mismatch of the hydrophobic helical length between the two components was of four residues, the longest nanotube was generated. Correspondingly, the hydrophobic helical segments have to interdigitate with an anti-parallel orientation at the hydrophobic core region of the nanotube. Copyright (C) 2010 European Peptide Society and John Wiley & Sons, Ltd.