Peptide flat-rod formation by precise arrangement among enantiomeric hydrophobic helices

Precise control of molecular arrangement is essential for functional molecular assemblies. A linear (I-shaped) amphiphilic block copolypeptide, polysarcosine-b-(l-Leu-Aib)₆ (I-SL12), which has a hydrophilic polysarcosine (PSar) chain and a hydrophobic helical block, was reported to self-assemble into nanotubes by regular packing of the Leu side chains. Here, we have synthesized a T-shaped amphiphilic block copolypeptide, (l-Leu-Aib)₃-AzF(PSar)-Aib-(l-Leu-Aib)₂ (T-SL12), to investigate the effect of molecular geometry on the morphology of molecular assemblies. Unlike conventional I-SL12, T-SL12 self-assembles into helical nanotubes. A mixture of T-SL12 (a right-handed helix) and polysarcosine-b-(d-Leu-Aib)₆ (I-SdL12, a left-handed helix) formed flat rod-shaped structures, while the mixture of T-SL12 and I-SL12 (both right-handed) forms nanotubes with an 80-nm diameter. This result indicates that stereo-complexes was formed between T-SL12 and I-SdL12. Peptidic flat-rod were obtained at ratios of T-SL12 and I-SdL12 from 1:1 to 1:3 (wt/wt), although their width (ca. 12 nm) and length (50-200 nm) did not change with stoichiometry. The thickness (6 nm) of the flat rod was measured by AFM. From these dimensions, we propose that the minor axis of peptidic flat-rod is composed of two stereo-complexed heterodimers of T-SL12 and I-SdL12 by orienting the I-SdL12s facing each other, and that this four-peptide unit is repeated side-by-side along the long axis.