Self-assembling cyclopeptides: From cylindrical dimers to nanotubes.

摘要

Self-assembling cyclopeptides composed of a chain of amino acids with alternating D- and L-configuration have found manifold applications in the arena of nanoworld applications. Selective backbone N-alkylation of every other amino acid residue was shown by Lorenzi et.al. to limit self-assembly of D,L-cyclopeptides to organic soluble nanocylindrical peptide dimers. These allow the examination of the molecular basis for the mutual affinity between the cyclic peptides, the subject of the first part of this thesis. After a study on the scope and limitations of peptide backbone modification for the formation of nanocylindrical β-sheet dimers, a new generation of backbone-modified D,L-cyclopeptides was designed, synthesized, and characterized that were thought to impart ion selectivity and channel rectification or gating to ion channels formed from non-substituted D,L-cyclopeptides in lipid bilayers. Selective switching of aggregation state was possible with the first photoswitchable D,L-cyclopeptide dimer, whose alkali metal ion binding was studied by proton NMR. Finally, backbone-modified D, L-cyclopeptides were shown to function as alkali metal ion carriers through bulk liquid membranes, thereby extending the potential utility of such structures to biological relevant settings.; A strategy for the design and synthesis of nanotubes with aromatic walls is detailed in the second part of this thesis. Such nanotubular arrays would have hydrophobic interiors with potential for new materials with unusual optical, electronic, or magnetic properties. A cyclic tetramer of 4-aminomethylphenylacetic acid was found to satisfy design constraints imposed by the self-assembly strategy pursued. During the synthesis of this building block, a new rearrangement was found, the use of the 4-methoxybenzyl group as a peptide backbone protecting group demonstrated, and a novel HPLC purification method for poorly soluble, hydrophobic molecules was developed. Structural studies support the self-assembly of this cyclic tetramer into nanotubes, as predicted by the design.